Ribozimlar sahifasining manbasini koʻrish

{{short description|RNK molekulalarining turi}}
[[Fayl:Full_length_hammerhead_ribozyme.png|thumb|[[Bolg'asimon ribozim|Bolg'asimon ribozimning]] 3D tuzilishi]]
'''Ribozimlar''' ('''ribo'''nuklein kislota '''ferment'''lari) — [[oqsil]] [[Ferment|fermentlari]] faoliyatiga o‘xshash tarzda maxsus biokimyoviy reaksiyalarni, jumladan [[Gen ekspressiyasi|gen ekspressiyasidagi]] [[RNK splaysingi|RNK splaysingini]] [[Kataliz|katalizlash]] qobiliyatiga ega bo‘lgan [[RNK]] molekulalaridir. 1982-yilda ribozimlarning kashf etilishi RNK ham genetik material ([[DNK]] kabi), ham biologik katalizator (oqsillar kabi) bo‘lishi mumkinligini ko‘rsatdi va bu [[RNK dunyosi nazariyasi|RNK dunyosi nazariyasiga]] hissa qo‘shdi. Ushbu nazariya RNK [[So'nggi universal umumiy ajdod|o‘z-o‘zini replikatsiya qiluvchi prebiotik tizimlar]] evolyutsiyasida muhim rol o‘ynagan bo‘lishi mumkinligini taxmin qiladi.<ref name="pmid6297745">{{cite journal|vauthors=Kruger K, Grabowski PJ, Zaug AJ, Sands J, Gottschling DE, Cech TR|title=Self-splicing RNA: autoexcision and autocyclization of the ribosomal RNA intervening sequence of Tetrahymena|url=https://archive.org/details/sim_cell_1982-11_31_1/page/147|journal=Cell|volume=31|issue=1|pages=147–157|date=November 1982|pmid=6297745|doi=10.1016/0092-8674(82)90414-7|s2cid=14787080}}</ref>

Tabiiy yoki [[Yo'naltirilgan evolyutsiya|''in vitro'' sharoitda evolyutsiyalangan]] ribozimlarning eng keng tarqalgan faoliyati RNK va DNKning [[Bog' uzilishi|qirqilishi]] yoki [[Ligatsiya (molekulyar biologiya)|ulanisni]] hamda peptid bog‘larining hosil bo‘lishini o‘z ichiga oladi.<ref name="Fedor_2005">{{cite journal|vauthors=Fedor MJ, Williamson JR|title=The catalytic diversity of RNAs|journal=Nature Reviews. Molecular Cell Biology|volume=6|issue=5|pages=399–412|date=May 2005|pmid=15956979|doi=10.1038/nrm1647|s2cid=33304782}}</ref> Masalan, ma’lum bo‘lgan eng kichik ribozim (GUGGC-3') [[Fenilalanin|Fenilalanil]]-[[Adenozin monofosfat|Adenozin Monofosfat]] ishtirokida GCCU-3' ketma-ketligini [[Aminoatsillanish|aminoatsillashi]] mumkin.<ref>{{cite journal|vauthors=Yarus M|title=The meaning of a minuscule ribozyme|journal=Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences|volume=366|issue=1580|pages=2902–2909|date=October 2011|pmid=21930581|pmc=3158920|doi=10.1098/rstb.2011.0139}}</ref> [[Ribosoma]] ichida ribozimlar [[Translyatsiya (biologiya)|oqsil sintezi]] jarayonida aminokislotalarni bog‘lash uchun [[23S ribosomal RNK|katta subbirlik ribosomal RNKning]] bir qismi sifatida faoliyat ko‘rsatadi. Shuningdek, ular [[RNK splaysingi]], [[virus replikatsiyasi]] va [[transport RNK]] biosintezi kabi turli xil [[RNK protsessingi]] reaksiyalarida ishtirok etadilar. Ribozimlarga misol sifatida [[bolg'asimon ribozim]], [[VS ribozim]], [[Leadzyme|lidzim]] va [[Tog'nog'ichsimon ribozim|tog'nog'ichsimon ribozimni]] keltirish mumkin.

[[Abiogenez|Hayotning kelib chiqishini]] RNK dunyosi nazariyasi orqali o‘rganayotgan tadqiqotchilar o‘z-o‘zini replikatsiya qilish qobiliyatiga ega bo‘lgan ribozimni kashf etish ustida ishlamoqdalar. Bu qobiliyat RNK polimerlarini katalitik sintez qilishni talab etadi. Bu jarayon prebiotik jihatdan ishonchli sharoitlarda, ma’lumotlarning degradatsiyasini oldini olish uchun yuqori nusxalash aniqligi bilan amalga oshishi kerak, shu bilan birga [[Evolyutsion ta'limot tarixi|Darvin evolyutsiyasi]] davom etishi uchun nusxalash jarayonida vaqti-vaqti bilan xatolar yuzaga kelishiga imkon berishi lozim.<ref name="Martin_2015">{{cite journal|vauthors=Martin LL, Unrau PJ, Müller UF|title=RNA synthesis by in vitro selected ribozymes for recreating an RNA world|journal=Life|location=Basel, Switzerland|volume=5|issue=1|pages=247–68|date=January 2015|pmid=25610978|pmc=4390851|doi=10.3390/life5010247|bibcode=2015Life....5..247M|doi-access=free}}</ref>

Ribozimlarni terapevtik vositalar, aniq RNK ketma-ketliklarini qirqish uchun mo‘ljallangan fermentlar, [[Biosensor|biosensorlar]] sifatida hamda [[funksional genomika]] va genlarni aniqlashda qo‘llashga urinishlar qilingan.<ref name="Hean">{{cite book |year=2008 |chapter=The Hammerhead Ribozyme Revisited: New Biological Insights for the Development of Therapeutic Agents and for Reverse Genomics Applications |editor=Morris KL |title=RNA and the Regulation of Gene Expression: A Hidden Layer of Complexity |publisher=Caister Academic Press |location=Norfolk, England |isbn=978-1-904455-25-7 |vauthors=Hean J, Weinberg MS |chapter-url=http://www.horizonpress.com/rnareg}}</ref>

== Kashf etilishi ==
[[Fayl:Ribozyme.jpg|right|thumb|300x300px|Ribozim tomonidan RNK qirqilishining sxemasi]]
Ribozimlar kashf etilishidan oldin, faqat katalitik [[Oqsil|oqsillar]] sifatida ta’riflangan [[Ferment|fermentlar]] yagona ma’lum biologik [[Kataliz|katalizatorlar]] hisoblangan. 1967-yilda [[Carl Woese]], [[Francis Crick]] va [[Leslie Orgel]] birinchi bo‘lib RNK katalizator sifatida harakat qilishi mumkinligini taxmin qilishgan. Bu g‘oya RNKning murakkab [[Ikkilamchi tuzilma|ikkilamchi tuzilmalar]] hosil qila olishi haqidagi kashfiyotga asoslangan edi.<ref>{{cite book |date=1967 |title=The Genetic Code |url=https://archive.org/details/geneticcodemolec00woes |publisher=Harper and Row |location=New York |vauthors=Woese C}}</ref> Ushbu ribozimlar RNK transkriptining [[Intron|intronida]] topilgan bo‘lib, u o‘zini transkriptdan olib tashlagan, shuningdek, pre-[[TRNK|tRNKlarning]] yetilishida ishtirok etuvchi RNKaza P kompleksining RNK tarkibiy qismida ham aniqlangan. 1989-yilda [[Thomas R. Cech]] va [[Sidney Altman]] "RNKning katalitik xususiyatlarini kashf etganliklari" uchun [[Kimyo]] bo‘yicha [[Nobel mukofoti|Nobel mukofotini]] bo‘lishib oldilar.<ref>[https://www.nobelprize.org/prizes/chemistry/1989/summary/ The Nobel Prize in Chemistry 1989] was awarded to [[Thomas R. Cech]] and [[Sidney Altman]] "for their discovery of catalytic properties of RNA".</ref> ''Ribozim'' atamasi ilk bor Kelly Kruger va boshqalar tomonidan 1982-yilda ''[[Cell (jurnal)|Cell]]'' jurnalida chop etilgan maqolada kiritilgan.<ref name="pmid6297745" />

[[Biologiya|Biologiyada]] kataliz faqat oqsillar uchun xos degan qat’iy ishonch mavjud edi. Biroq, RNK katalizi g‘oyasi qisman hayotning kelib chiqishi haqidagi qadimiy savol bilan bog‘liq edi: Qaysi biri birinchi paydo bo‘lgan, hujayra ishini bajaradigan fermentlarmi yoki fermentlarni ishlab chiqarish uchun zarur bo‘lgan ma’lumotni tashuvchi nuklein kislotalarmi? "Ribonuklein kislotalar katalizator sifatida" tushunchasi bu muammoni chetlab o‘tadi. RNK, mohiyatan, ham tovuq, ham tuxum bo‘lishi mumkin.<ref name="pmid6205343">{{cite journal|vauthors=Visser CM|title=Evolution of biocatalysis 1. Possible pre-genetic-code RNA catalysts which are their own replicase|journal=Origins of Life|volume=14|issue=1–4|pages=291–300|year=1984|pmid=6205343|doi=10.1007/BF00933670|s2cid=31409366|bibcode=1984OrLi...14..291V}}</ref>

1980-yillarda Thomas Cech [[Kolorado Boulder universiteti|Kolorado Boulder universitetida]] ''[[Tetrahymena thermophila]]''dagi ribosomal RNK genidagi [[Intron|intronlarning]] kesib olinishini o‘rganayotgan edi. Splaysing reaksiyasi uchun mas’ul fermentni tozalashga urinayotganda, u intron hech qanday hujayra ekstrakti qo‘shilmagan holda ham kesib olinishi mumkinligini aniqladi. Qanchalik urinishmasin, Cech va uning hamkasblari splaysing reaksiyasi bilan bog‘liq hech qanday oqsilni aniqlay olmadilar. Ko‘p izlanishlardan so‘ng, Cech RNKning intron ketma-ketligi qismi [[fosfodiester]] bog‘larni uzishi va qayta tiklashi mumkinligini taklif qildi. Taxminan shu vaqtda, [[Yel universiteti]] professori Sidney Altman hujayrada tRNK molekulalarining qayta ishlanishini o‘rganayotgan edi. U va uning hamkasblari prekursur [[TRNK|tRNKni]] faol tRNKga aylantirishga mas’ul bo‘lgan [[Ribonukleaza P|RNKaza-P]] deb ataladigan fermentni ajratib olishdi. Ular hayrat bilan shuni aniqladilarki, RNKaza-P oqsilga qo‘shimcha ravishda RNKni ham o‘z ichiga oladi va RNK faol fermentning muhim tarkibiy qismi hisoblanadi. Bu shunchalik g‘ayrioddiy g‘oya ediki, ular o‘z natijalarini nashr etishda qiyinchiliklarga duch kelishdi. Keyingi yili{{Which|date=January 2023}}, Altman RNKaza-P ning RNK subbirligi hech qanday oqsil komponenti ishtirokisiz prekursur tRNKni faol tRNKga aylantirishni katalizlashi mumkinligini ko‘rsatib, RNK katalizator sifatida harakat qila olishini isbotladi.

Cech va Altmanning kashfiyotidan beri boshqa tadqiqotchilar o‘z-o‘zini qirquvchi RNK yoki katalitik RNK molekulalarining boshqa misollarini topdilar. Ko‘plab ribozimlar tog‘nog‘ichsimon yoki bolg‘asimon shakldagi faol markazga va boshqa RNK molekulalarini maxsus ketma-ketliklarda qirqish imkonini beruvchi noyob ikkilamchi tuzilishga ega. Hozirda har qanday RNK molekulasini maxsus qirqadigan ribozimlarni yaratish mumkin. Ushbu RNK katalizatorlari farmatsevtikada qo‘llanilishi mumkin. Masalan, [[OIV]] (HIV) RNKsini qirqish uchun mo‘ljallangan ribozim loyihalashtirilgan. Agar shunday ribozim hujayra tomonidan ishlab chiqarilsa, kirib kelayotgan barcha virus zarralarining RNK genomi ribozim tomonidan qirqilib, infeksiyaning oldini olgan bo‘lardi.

== Tuzilishi va mexanizmi ==
Oqsillarda topiladigan 20 ta aminokislota [[Yon zanjir|yon zanjirlariga]] nisbatan har bir monomer birligi (nukleotidlar) uchun atigi to‘rtta tanlov mavjudligiga qaramay, ribozimlar turli xil tuzilmalar va mexanizmlarga ega. Ko‘p hollarda ular o‘zlarining oqsil muqobillari foydalanadigan mexanizmga taqlid qilishga qodir. Masalan, o‘z-o‘zini qirquvchi ribozim RNKlarida, nukleofil sifatida 2' gidroksil guruhi ko‘prik hosil qiluvchi fosfatga hujum qiladi va N+1 asosining 5' kislorodi chiqib ketuvchi guruh sifatida harakatlanishi orqali in-line SN2 reaksiyasi amalga oshiriladi. Taqqoslash uchun, xuddi shu reaksiyani katalizlaydigan RNKaza A oqsili fosfat asosiga hujum qilish uchun asos sifatida muvofiqlashtiruvchi gistidin va lizindan foydalanadi.<ref name="Fedor_2005" />{{clarify|reason=**This is example is not clear can someone please translate to layman's terms?**"For example, self cleaving ribozyme RNAs and RNase A proteins both cleave phosphate backbones. However, the mechanisms differs. While the RNase A protein uses a coordinating histidine and lysine to attack the backbone, self cleaving ribozyme RNAs carry out an in-line SN2 reaction using the 2' hydroxyl group as a nucleophile attacking the bridging phosphate and causing 5' oxygen of the N+1 base to act as a leaving group."|date=April 2018}}

Ko‘pgina oqsil fermentlari kabi, metall bog‘lanishi ham ko‘plab ribozimlarning faoliyati uchun juda muhimdir.<ref>{{cite journal|vauthors=Pyle AM|title=Ribozymes: a distinct class of metalloenzymes|url=https://archive.org/details/sim_science_1993-08-06_261_5122/page/708|journal=Science|volume=261|issue=5122|pages=709–714|date=August 1993|pmid=7688142|doi=10.1126/science.7688142|bibcode=1993Sci...261..709P}}</ref> Ko‘pincha bu o‘zaro ta’sirlar fosfat asosi va nukleotid asosi bilan birgalikda kuchli konformatsion o‘zgarishlarni keltirib chiqaradi.<ref>{{cite journal|vauthors=Freisinger E, Sigel RK|year=2007|title=From nucleotides to ribozymes—A comparison of their metal ion binding properties|url=https://www.zora.uzh.ch/id/eprint/59908/1/ZORA_.59908_FromNucleotidesToRibozymes.pdf|journal=Coord. Chem. Rev.|volume=251|issue=13–14|pages=1834–1851|doi=10.1016/j.ccr.2007.03.008}}{{Oʻlikhavola|date=may 2026 |bot=InternetArchiveBot |fix-attempted=yes }}</ref> Metall ishtirokida fosfodiester asosini qirqish uchun ikkita mexanizm sinfi mavjud. Birinchi mexanizmda, ichki 2'-OH guruhi fosfor markaziga SN<sub>2</sub> mexanizmi bo‘yicha hujum qiladi. Metall ionlari avval fosfat kislorodini muvofiqlashtirish va keyinchalik oksianionni barqarorlashtirish orqali ushbu reaksiyani rag‘batlantiradi. Ikkinchi mexanizm ham SN<sub>2</sub> siljishiga amal qiladi, ammo nukleofil RNKning o‘zidan emas, balki suv yoki tashqi gidroksil guruhlaridan keladi. Eng kichik ribozim UUU bo‘lib, u Mn<sup>2+</sup> ishtirokida birinchi mexanizm orqali GAAA tetranukleotidining G va A orasidagi qirqilishini rag‘batlantirishi mumkin. Ushbu trinukleotidning (komplementar tetramer o‘rniga) ushbu reaksiyani katalizlashining sababi shundaki, UUU-AAA juftligi 64 ta konformatsiya orasida eng kuchsiz va eng egiluvchan trinukleotid bo‘lib, bu Mn<sup>2+</sup> uchun bog‘lanish joyini ta’minlaydi.<ref name=":0">{{cite journal|vauthors=Pyle AM|title=Ribozymes: a distinct class of metalloenzymes|url=https://archive.org/details/sim_science_1993-08-06_261_5122/page/708|journal=Science|volume=261|issue=5122|pages=709–714|date=August 1993|pmid=7688142|doi=10.1126/science.7688142|bibcode=1993Sci...261..709P|jstor=2882234}}</ref>

Fosforil o‘tkazilishi metall ionlarisiz ham katalizlanishi mumkin. Masalan, oshqozon osti bezi ribonukleazasi A va [[gepatit delta virusi]] (HDV) ribozimlari metall ionlarisiz kislota-asos katalizi orqali RNK asosining qirqilishini katalizlashi mumkin.<ref name=":2">{{cite journal|vauthors=Lilley DM|title=Mechanisms of RNA catalysis|journal=Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences|volume=366|issue=1580|pages=2910–2917|date=October 2011|pmid=21930582|pmc=3158914|doi=10.1098/rstb.2011.0132|jstor=23035661}}</ref><ref name=":1">{{cite journal|vauthors=Doudna JA, Cech TR|title=The chemical repertoire of natural ribozymes|url=https://archive.org/details/sim_nature-uk_2002-07-11_418_6894/page/222|journal=Nature|volume=418|issue=6894|pages=222–228|date=July 2002|pmid=12110898|doi=10.1038/418222a|s2cid=4417095|bibcode=2002Natur.418..222D}}</ref> Tog‘nog‘ichsimon ribozim ham metall ionlarisiz RNKning o‘z-o‘zini qirqishini katalizlashi mumkin, ammo buning mexanizmi hali ham noaniq.<ref name=":1" />

Ribozim, shuningdek, faollanish entropiyasini pasaytirish orqali qo‘shni aminokislotalar o‘rtasida peptid bog‘ining hosil bo‘lishini katalizlashi mumkin.<ref name=":2" />
[[Fayl:Ribozyme_structure_picutres.png|alt=Ribozyme structure pictures|center|thumb|550x550px|Ribozim tuzilmalarining xilma-xilligini ko‘rsatuvchi tasvir. Chapdan o‘ngga: lidzim (leadzyme), bolg‘asimon ribozim, tvister ribozim]]

== Faoliyati ==
[[Fayl:Protein_translation.gif|thumb|250x250px|[[Ribosoma]] — bu RNKni oqsillarga [[Translyatsiya (biologiya)|translyatsiya]] qilish uchun ribozimdan foydalanadigan [[biologik mashina]].]]
Garchi ribozimlar ko‘pchilik hujayralarda juda kam uchrasa-da, ularning roli ba’zan hayot uchun o‘ta muhimdir. Masalan, RNKni oqsillarga [[Translyatsiya (biologiya)|translyatsiya]] qiluvchi [[biologik mashina]] — [[Ribosoma|ribosomaning]] funksional qismi asosan ribozim bo‘lib, u ko‘pincha [[Kofaktor (biokimyo)|kofaktor]] sifatida [[Mg2+|Mg]]<sup>2+</sup> kabi metall ionlari bilan muvofiqlashtirilgan [[RNK uchlamchi tuzilishi|RNK uchlamchi tuzilish motivlaridan]] tashkil topgan.<ref>{{cite journal|vauthors=Ban N, Nissen P, Hansen J, Moore PB, Steitz TA|title=The complete atomic structure of the large ribosomal subunit at 2.4 A resolution|url=https://archive.org/details/sim_science_2000-08-11_289_5481/page/904|journal=Science|volume=289|issue=5481|pages=905–920|date=August 2000|pmid=10937989|doi=10.1126/science.289.5481.905|citeseerx=10.1.1.58.2271|bibcode=2000Sci...289..905B}}</ref> Model tizimda, C3 ribozimining qisqartirilishi orqali yaratilgan katalizator/substrat ishtirokida, katalizator bilan 3 ta asos juftligi komplementar bo‘lgan to‘rt nukleotidli substratning ''trans''-[[Fenilalanin|fenilalaninlanishini]] katalizlovchi besh nukleotidli RNKda [[ikki valentli]] [[Kation|kationlarga]] ehtiyoj yo‘q.<ref name="pmid20176971">{{cite journal|vauthors=Turk RM, Chumachenko NV, Yarus M|title=Multiple translational products from a five-nucleotide ribozyme|journal=Proceedings of the National Academy of Sciences of the United States of America|volume=107|issue=10|pages=4585–4589|date=March 2010|pmid=20176971|pmc=2826339|doi=10.1073/pnas.0912895107|doi-access=free|bibcode=2010PNAS..107.4585T}}</ref>

Eng yaxshi o‘rganilgan ribozimlar, ehtimol, Cech<ref>{{cite journal|vauthors=Cech TR|title=Structural biology. The ribosome is a ribozyme|url=https://archive.org/details/sim_science_2000-08-11_289_5481/page/878|journal=Science|volume=289|issue=5481|pages=878–879|date=August 2000|pmid=10960319|doi=10.1126/science.289.5481.878|s2cid=24172338}}</ref> va Altman<ref>{{cite journal|vauthors=Altman S|title=Nobel lecture. Enzymatic cleavage of RNA by RNA|journal=Bioscience Reports|volume=10|issue=4|pages=317–337|date=August 1990|pmid=1701103|doi=10.1007/BF01117232|s2cid=12733970}}</ref> tomonidan qilingan dastlabki kashfiyotlardagi kabi o‘zini yoki boshqa RNKlarni kesuvchi ribozimlardir. Biroq, ribozimlar turli reaksiyalarni katalizlash uchun loyihalashtirilishi mumkin<ref>{{cite journal|vauthors=Walter NG, Engelke DR|title=Ribozymes: catalytic RNAs that cut things, make things, and do odd and useful jobs|journal=Biologist|volume=49|issue=5|pages=199–203|date=October 2002|pmid=12391409|pmc=3770912}}</ref> yoki ular tabiiy ravishda shunday xususiyatga ega bo‘ladi. Ushbu faoliyat turlariga quyidagilar kiradi:<ref>{{Cite journal|last=Lamond|first=A. I.|date=June 1989|title=Tetrahymena telomerase contains an internal RNA template|journal=Trends in Biochemical Sciences|volume=14|issue=6|pages=202–204|doi=10.1016/0968-0004(89)90022-4|issn=0968-0004|pmid=2474873}}</ref>

* [[RNK endonukleaza]]
* [[Nukleotidiltransferaza]]
* [[Fosfotransferaza]]
* [[Fosfataza]]
* [[Ligaza]]
* [[Kinaza]]
* Glyukanotransferaza

RNK [[Prion|prionning]] patologik [[Kimyoviy konformatsiya|oqsil konformatsiyasini]] [[Shaperon (oqsil)|shaperoninga]] o‘xshash tarzda [[Oqsil buklanishi|buklanishini]] katalizlashi mumkin.<ref name="pmid15014886">{{cite journal|vauthors=Supattapone S|title=Prion protein conversion in vitro|journal=Journal of Molecular Medicine|volume=82|issue=6|pages=348–356|date=June 2004|pmid=15014886|doi=10.1007/s00109-004-0534-3|s2cid=24908667}}</ref>

== Ribozimlar va hayotning kelib chiqishi ==
RNK shuningdek, irsiy molekula sifatida harakat qilishi mumkin, bu [[Walter Gilbert|Walter Gilbertni]] uzoq o‘tmishda [[Hujayra (biologiya)|hujayra]] RNKdan ham genetik material, ham strukturaviy va katalitik molekula sifatida foydalanganligini, ya'ni bugungi kunda bo‘lgani kabi bu funksiyalarni [[DNK]] va [[oqsil]] o‘rtasida taqsimlamaganligini taklif qilishga undadi; bu gipoteza [[hayotning kelib chiqishi]] haqidagi "[[RNK dunyosi nazariyasi]]" sifatida tanilgan.<ref>{{cite journal|vauthors=Gilbert W|title=Origin of life: The RNA world|url=https://archive.org/details/sim_nature-uk_1986-02-20_319_6055/page/618|journal=Nature|volume=319|issue=6055|pages=618|date=1986|doi=10.1038/319618a0|bibcode=1986Natur.319..618G|s2cid=8026658|doi-access=free}}</ref> [[Nukleotid|Nukleotidlar]] va [[RNK]] (va shuning uchun ribozimlar) noorganik kimyoviy moddalardan paydo bo‘lishi mumkinligi sababli, ular birinchi [[Ferment|fermentlarga]] nomzodlar va aslida birinchi "replikatorlar" (ya'ni, o‘zini o‘zi nusxalovchi axborot tashuvchi makromolekulalar) hisoblanadi. O‘zining aniq nusxasini yaratish uchun ikkita substratni ulaydigan o‘z-o‘zini replikatsiya qiluvchi ribozim misoli 2002-yilda tasvirlangan.<ref>{{cite journal|vauthors=Paul N, Joyce GF|title=A self-replicating ligase ribozyme|journal=Proceedings of the National Academy of Sciences of the United States of America|volume=99|issue=20|pages=12733–12740|date=October 2002|pmid=12239349|pmc=130529|doi=10.1073/pnas.202471099|doi-access=free|bibcode=2002PNAS...9912733P}}</ref> RNKning katalitik faolligining kashf etilishi hayotning kelib chiqishidagi "tovuq va tuxum" paradoksini hal qildi va peptid hamda nuklein kislotaning [[Molekulyar biologiyaning markaziy dogmasi|markaziy dogmasi]] kelib chiqishi muammosini yechdi. Ushbu ssenariyga ko‘ra, hayot paydo bo‘lishida barcha fermentativ faollik va genetik ma’lumotlarni kodlash bitta molekula: RNK tomonidan amalga oshirilgan.

[[Laboratoriya|Laboratoriyada]] juda maxsus sharoitlarda faollashtirilgan [[Monomer|monomerlardan]] boshqa RNK molekulalarini sintez qilishni katalizlashga qodir bo‘lgan ribozimlar ishlab chiqarilgan bo‘lib, bu molekulalar [[RNK polimeraza]] ribozimlari deb ataladi.<ref name="pmid11358999">{{cite journal|vauthors=Johnston WK, Unrau PJ, Lawrence MS, Glasner ME, Bartel DP|title=RNA-catalyzed RNA polymerization: accurate and general RNA-templated primer extension|url=https://archive.org/details/sim_science_2001-05-18_292_5520/page/1318|journal=Science|volume=292|issue=5520|pages=1319–1325|date=May 2001|pmid=11358999|doi=10.1126/science.1060786|s2cid=14174984|citeseerx=10.1.1.70.5439|bibcode=2001Sci...292.1319J}}</ref> Birinchi RNK polimeraza ribozimi 1996-yilda xabar qilingan va uzunligi 6 nukleotidgacha bo‘lgan RNK polimerlarini sintez qilishga qodir edi.<ref name="Ekland_1996">{{cite journal|vauthors=Ekland EH, Bartel DP|title=RNA-catalysed RNA polymerization using nucleoside triphosphates|url=https://archive.org/details/sim_nature-uk_1996-07-25_382_6589/page/372|journal=Nature|volume=382|issue=6589|pages=373–6|date=July 1996|pmid=8684470|doi=10.1038/382373a0|bibcode=1996Natur.382..373E|s2cid=4367137}}</ref> Tasodifiy RNK ketma-ketliklarining katta to‘plamidan olingan RNK ligaza ribozimida [[Mutagenez]] va saralash o‘tkazildi,<ref name="Bartel_1993">{{cite journal|vauthors=Bartel DP, Szostak JW|title=Isolation of new ribozymes from a large pool of random sequences [see comment]|journal=Science|location=New York, N.Y.|volume=261|issue=5127|pages=1411–8|date=September 1993|pmid=7690155|doi=10.1126/science.7690155|url=https://archive.org/details/sim_science_1993-09-10_261_5127/page/1410}}</ref> natijada 2001-yilda "Round-18" polimeraza ribozimi ajratib olindi, bu endi uzunligi 14 nukleotidgacha bo‘lgan RNK polimerlarini katalizlashi mumkin edi.<ref name="Johnston_2001">{{cite journal|vauthors=Johnston WK, Unrau PJ, Lawrence MS, Glasner ME, Bartel DP|title=RNA-catalyzed RNA polymerization: accurate and general RNA-templated primer extension|url=https://archive.org/details/sim_science_2001-05-18_292_5520/page/1318|journal=Science|location=New York, N.Y.|volume=292|issue=5520|pages=1319–25|date=May 2001|pmid=11358999|doi=10.1126/science.1060786|bibcode=2001Sci...292.1319J|s2cid=14174984}}</ref> Round-18 ribozimida keyingi saralash qo‘llanilganda, B6.61 ribozimi hosil bo‘ldi va u fosfodiester bog‘larining uzilishi natijasida parchalangunga qadar, 24 soat ichida praymer shabloniga 20 tagacha [[nukleotid]] qo‘shishga muvaffaq bo‘ldi.<ref name="pmid17586759">{{cite journal|vauthors=Zaher HS, Unrau PJ|title=Selection of an improved RNA polymerase ribozyme with superior extension and fidelity|journal=RNA|volume=13|issue=7|pages=1017–1026|date=July 2007|pmid=17586759|pmc=1894930|doi=10.1261/rna.548807}}</ref>

Ribozimlar RNK ketma-ketligini polimerizatsiya qilish tezligi [[mitsella]] ichida sodir bo‘lganda sezilarli darajada oshadi.<ref name="Müller_2008">{{cite journal|vauthors=Müller UF, Bartel DP|title=Improved polymerase ribozyme efficiency on hydrophobic assemblies|journal=RNA|location=New York, N.Y.|volume=14|issue=3|pages=552–62|date=March 2008|pmid=18230767|pmc=2248263|doi=10.1261/rna.494508}}</ref>

Keyingi kashf etilgan ribozim "tC19Z" ribozimi bo‘lib, u 0,0083 mutatsiya/nukleotid aniqligi bilan 95 tagacha [[nukleotid]] qo‘sha oladi.<ref name="pmid21474753">{{cite journal|vauthors=Wochner A, Attwater J, Coulson A, Holliger P|title=Ribozyme-catalyzed transcription of an active ribozyme|url=https://archive.org/details/sim_science_2011-04-08_332_6026/page/208|journal=Science|volume=332|issue=6026|pages=209–212|date=April 2011|pmid=21474753|doi=10.1126/science.1200752|s2cid=39990861|bibcode=2011Sci...332..209W}}</ref> Keyinchalik tadqiqotchilar tomonidan "tC9Y" ribozimi kashf qilindi, u noldan past haroratdagi evtektik faza sharoitida uzunligi 206 nukleotidgacha bo‘lgan RNK zanjirlarini sintez qilishga qodir edi.<ref name="Attwater_2013">{{cite journal|vauthors=Attwater J, Wochner A, Holliger P|title=In-ice evolution of RNA polymerase ribozyme activity|journal=Nature Chemistry|volume=5|issue=12|pages=1011–8|date=December 2013|pmid=24256864|pmc=3920166|doi=10.1038/nchem.1781|bibcode=2013NatCh...5.1011A}}</ref> Bunday sharoitlar avvalroq ribozim polimeraza faoliyatini rag‘batlantirishi ko‘rsatilgan edi.<ref name="Attwater_2010">{{cite journal|vauthors=Attwater J, Wochner A, Pinheiro VB, Coulson A, Holliger P|title=Ice as a protocellular medium for RNA replication|journal=Nature Communications|volume=1|issue=6|article-number=76|date=September 2010|pmid=20865803|doi=10.1038/ncomms1076|bibcode=2010NatCo...1...76A|doi-access=free}}</ref>

tC9-4M deb nomlangan RNK polimeraza ribozimi (RPR) fiziologik darajaga yaqin magniy ioni kontsentratsiyasida o‘zidan uzunroq (ya'ni 177 nt dan uzun) RNK zanjirlarini polimerizatsiya qila oldi, oldingi RPRlar esa 200 mM gacha bo‘lgan prebiotik jihatdan ishonchsiz kontsentratsiyalarni talab qilardi. Bunga erishish uchun talab qilingan yagona omil lizin dekapeptidi deb ataladigan juda oddiy aminokislota polimerining mavjudligi edi.<ref name="Tagami_2017">{{cite journal|vauthors=Tagami S, Attwater J, Holliger P|title=Simple peptides derived from the ribosomal core potentiate RNA polymerase ribozyme function|journal=Nature Chemistry|volume=9|issue=4|pages=325–332|date=April 2017|pmid=28338682|pmc=5458135|doi=10.1038/nchem.2739|bibcode=2017NatCh...9..325T}}</ref>

O‘sha vaqtgacha sintez qilingan eng murakkab RPR 24-3 deb nomlangan bo‘lib, u turli xil nukleotid ketma-ketliklarini polimerizatsiya qilish va oldingi ribozimlar uchun erishib bo‘lmaydigan RNK substratlarining murakkab ikkilamchi tuzilmalarida harakatlanish qobiliyatiga ega edi. Aslida, bu tajriba tRNK molekulasini sintez qilish uchun ribozimdan foydalanilgan birinchi holat bo‘ldi.<ref name="Horning_2016">{{cite journal|vauthors=Horning DP, Joyce GF|title=Amplification of RNA by an RNA polymerase ribozyme|journal=Proceedings of the National Academy of Sciences of the United States of America|volume=113|issue=35|pages=9786–91|date=August 2016|pmid=27528667|pmc=5024611|doi=10.1073/pnas.1610103113|bibcode=2016PNAS..113.9786H|doi-access=free}}</ref> 24-3 ribozimidan boshlab, Tjhung va boshqalar<ref name="Tjhung_2020">{{cite journal|vauthors=Tjhung KF, Shokhirev MN, Horning DP, Joyce GF|title=An RNA polymerase ribozyme that synthesizes its own ancestor|journal=Proceedings of the National Academy of Sciences of the United States of America|volume=117|issue=6|pages=2906–2913|date=February 2020|pmid=31988127|pmc=7022166|doi=10.1073/pnas.1914282117|bibcode=2020PNAS..117.2906T|doi-access=free}}</ref> '38-6' deb nomlangan RNK polimeraza ribozimini olish uchun [[Yo'naltirilgan evolyutsiya|''in vitro'' evolyutsiyaning]] yana o‘n to‘rt bosqichini qo‘lladilar, bu ribozim murakkab RNK molekulalarini nusxalashda misli ko‘rilmagan faollik darajasiga ega edi. Biroq, bu ribozim o‘zini nusxalay olmaydi va uning RNK mahsulotlari yuqori [[Mutatsiya tezligi|mutatsiya tezligiga]] ega. Keyingi tadqiqotda olimlar 38-6 ribozimidan boshlab, '52-2' ribozimini yaratish uchun yana 14 ta saralash bosqichini qo‘lladilar. 38-6 bilan taqqoslaganda, u bir necha barobar faolroq bo‘lib, I toifali ligazaning aniqlanadigan va funksional darajalarini hosil qilishni boshlashi mumkin edi, garchi u hali ham T7 RNK polimeraza kabi oqsillar tomonidan xuddi shu shablonni nusxalashga nisbatan aniqlik va funksionallikda cheklangan edi.<ref>{{cite journal|vauthors=Portillo X, Huang YT, Breaker RR, Horning DP, Joyce GF|date=2021|title=Witnessing the structural evolution of an RNA enzyme.|journal=eLife|volume=10|article-number=e71557|doi=10.7554/eLife.71557|pmid=34498588|pmc=8460264|doi-access=free}}</ref>

t5(+1) deb ataladigan RPR bir vaqtning o‘zida bitta nukleotid emas, balki triplet nukleotidlarni qo‘shadi. Ushbu geterodimer RPR 24-3 uchun erishib bo‘lmaydigan ikkilamchi tuzilmalarda, shu jumladan shpilkalarda harakatlana oladi. Avval sintez qilingan Z RPR deb nomlanuvchi RPRdan olingan RNK variantlarining dastlabki to‘plamida ikki ketma-ketlik alohida paydo bo‘lib, o‘zaro bog‘liq bo‘lib evolyutsiyalandi. 1-turdagi RNK katalitik jihatdan nofaol bo‘lib rivojlandi, ammo 5-turdagi RNK bilan kompleks hosil qilishi uning polimerizatsiya qobiliyatini kuchaytirdi va RNK shablon substrati bilan molekulalararo o‘zaro ta’sirlarni amalga oshirishga imkon berdi, bu esa shablonni to‘g‘ridan-to‘g‘ri RPRning RNK ketma-ketligiga bog‘lash zaruratini yo‘qotdi (bu oldingi tadqiqotlarning cheklovi edi). t5(+1) nafaqat shablonga bog‘lanishni talab qilmadi, balki praymer ham kerak emas edi, chunki t5(+1) shablonni ham 3' → 5', ham 5' 3 → 3' yo‘nalishlarida polimerizatsiya qilish qobiliyatiga ega edi.<ref name="Attwater_2018">{{cite journal|vauthors=Attwater J, Raguram A, Morgunov AS, Gianni E, Holliger P|title=Ribozyme-catalysed RNA synthesis using triplet building blocks|journal=eLife|volume=7|issue=|date=May 2018|article-number=e35255|pmid=29759114|pmc=6003772|doi=10.7554/eLife.35255|doi-access=free}}</ref>

Yuqori darajada rivojlangan{{Vague|reason=What does "highly evolved" mean? Strange phrasing.|date=April 2022}} RNK polimeraza ribozimi [[revers transkriptaza]] (teskari transkriptaza) sifatida ishlashga, ya'ni RNK shablonidan foydalanib DNK nusxasini sintez qilishga qodir edi.<ref name="Samanta_2017">{{cite journal|vauthors=Samanta B, Joyce GF|title=A reverse transcriptase ribozyme|journal=eLife|volume=6|issue=|date=September 2017|article-number=e31153|pmid=28949294|pmc=5665644|doi=10.7554/eLife.31153|doi-access=free}}</ref> Bunday faoliyat{{By whom|date=April 2022}} yerdagi hayotning dastlabki tarixida RNKdan DNK genomlariga o‘tishda hal qiluvchi ahamiyatga ega bo‘lgan deb hisoblanadi. Teskari transkripsiya qobiliyati dastlabki RNKga bog‘liq RNK polimeraza ribozimining ikkilamchi funksiyasi sifatida paydo bo‘lgan bo‘lishi mumkin.

Ribozimga aylanadigan RNK ketma-ketligi duplekslangan RNKga bostirib kirib, ochiq golopolimeraza kompleksiga qayta joylashishga, so‘ngra maxsus RNK promotor ketma-ketligini qidirishga va aniqlangandan so‘ng, ketma-ketlikning komplementar zanjirini polimerizatsiya qiluvchi protsessiv shaklga yana qayta joylashishga qodir. Ushbu ribozim duplekslangan RNKni 107 nukleotidgacha uzaytirishga qodir va buni polimerizatsiya qilinayotgan ketma-ketlikni bog‘lashga ehtiyoj sezmasdan amalga oshiradi.<ref name="pmid33737482">{{cite journal|vauthors=Cojocaru R, Unrau PJ|title=Processive RNA polymerization and promoter recognition in an RNA World|url=https://archive.org/details/science_2021-03-19_371_6535/page/1225|journal=Science|volume=371|issue=6535|pages=1225–1232|date=March 2021|pmid=33737482|doi=10.1126/science.abd9191|bibcode=2021Sci...371.1225C|s2cid=232271298}}</ref>

Qisqa 20 [[Nukleotid|nukleotidli]] RNK varianti ribozimi aniqlandi, u ikkita 10 nukleotidli [[Oligomer|oligomerlarning]] shablon yo‘naltirilgan ligatsiyasi orqali o‘z-o‘zini qayta ishlab chiqaradi.<ref name="Mizuuchi2023">{{cite journal|vauthors=Mizuuchi R, Ichihashi N|title=Minimal RNA self-reproduction discovered from a random pool of oligomers|journal=Chem Sci|volume=14|issue=28|pages=7656–7664|date=July 2023|pmid=37476714|doi=10.1039/d3sc01940c|url=|pmc=10355099}}</ref> RNKning o‘z-o‘zini qayta ishlab chiqarishining ushbu minimal turi oligomerlarning tasodifiy to‘plamida kashf etilgan va ibtidoiy tarkibiy qismlardan RNKga asoslangan genetik tizimning paydo bo‘lishidagi dastlabki qadam bo‘lishi mumkin.<ref name="Mizuuchi2023" />

== Ribozimga asoslangan jinsiy ko‘payishning kelib chiqishi ==
Jinsiy ko‘payish DNK hujayrali hayot shakllaridan oldin mavjud bo‘lgan [[RNK dunyosi|RNK dunyosida]] bo‘lgan bo‘lishi mumkin.<ref>{{cite journal|pmid=6164094|volume=244|issue=4|title=The origin of genetic information|url=https://archive.org/details/sim_scientific-american_1981-04_244_4/page/88|date=April 1981|pages=88–92, 96, et passim|vauthors=[[Manfred Eigen|Eigen M]], Gardiner W, [[Peter Schuster (theoretical chemist)|Schuster P]], [[Ruthild Winkler|Winkler-Oswatitsch R]]|journal=Scientific American|doi=10.1038/scientificamerican0481-88|bibcode=1981SciAm.244d..88E}}</ref> Muhim RNK ribozim molekulalarining yagona nusxalariga ega genomli dastlabki hujayrali hayot shakllari muhim ribozimning replikatsiyasini bloklashi mumkin bo‘lgan, shu bilan hujayra o‘limiga olib keladigan atrof-muhitning zararli sharoitlariga nisbatan zaif bo‘lishi mumkin edi. Shunday shikastlangan ikkita dastlabki hujayraning birlashishi (jinsiy o‘zaro ta’sir) RNK segmentlarining shikastlanmagan kombinatsiyalarini birlashtirishga imkon beradi, bu esa funksional genom shakllanishini osonlashtiradi va hujayraning omon qolishi hamda ko‘payish qobiliyatini ta’minlaydi.

== Sun'iy ribozimlar ==
Tirik organizmlarda mavjud bo‘lgan ribozimlar kashf etilgandan beri, laboratoriyada yaratilgan yangi sintetik ribozimlarni o‘rganishga qiziqish paydo bo‘ldi. Masalan, sun’iy ravishda ishlab chiqarilgan, yaxshi fermentativ faollikka ega o‘z-o‘zini qirquvchi RNKlar yaratildi. Tang va Breaker<ref name="TangBreaker">{{cite journal|vauthors=Tang J, Breaker RR|title=Structural diversity of self-cleaving ribozymes|journal=Proceedings of the National Academy of Sciences of the United States of America|volume=97|issue=11|pages=5784–5789|date=May 2000|pmid=10823936|pmc=18511|doi=10.1073/pnas.97.11.5784|doi-access=free|bibcode=2000PNAS...97.5784T}}</ref> tasodifiy ketma-ketlikdagi RNKlardan kelib chiqqan RNKlarni ''in vitro'' tanlash orqali o‘z-o‘zini qirquvchi RNKlarni ajratib oldilar. Ishlab chiqarilgan ba’zi sintetik ribozimlar yangi tuzilishga ega bo‘lsa, ba’zilari tabiatda uchraydigan bolg‘asimon ribozimga o‘xshash edi.

2015-yilda [[Shimoli-g'arbiy universiteti]] va [[Illinoys universiteti Chikago]] tadqiqotchilari hujayra ichidagi barcha oqsillar va fermentlarni ishlab chiqaradigan haqiqiy hujayra komponenti kabi deyarli yaxshi ishlaydigan bog‘langan ribosomani ishlab chiqdilar. [[Ribosoma-T]] yoki Ribo-T deb ataladigan sun’iy ribosoma Michael Jewett va Alexander Mankin tomonidan yaratilgan.<ref>[http://www.northwestern.edu/newscenter/stories/2015/07/artificial-ribosomes.html#sthash.CiTI1pw3.dpuf Engineer and Biologist Design First Artificial Ribosome - Designer ribosome could lead to new drugs and next-generation biomaterials] published on July 31, 2015 by Northwestern University</ref> Sun’iy ribozimlarni yaratishda qo‘llaniladigan usullar yo‘naltirilgan evolyutsiyani o‘z ichiga oladi. Bu yondashuv RNKning ham katalizator, ham informatsion polimer sifatidagi ikki tomonlama tabiatidan foydalanadi, bu tadqiqotchiga [[polimeraza]] fermentlari yordamida RNK katalizatorlarining katta populyatsiyalarini ishlab chiqarishni osonlashtiradi. Ribozimlar [[revers transkriptaza]] yordamida turli xil [[CDNK|cDNKga]] (komplementar DNK) teskari transkripsiya qilish va [[Xatoga moyil PZR]] yordamida kuchaytirish orqali mutatsiyaga uchratiladi. Ushbu tajribalarda tanlash parametrlari ko‘pincha farq qiladi. [[Ligaza ribozim|Ligaza ribozimni]] tanlash usullaridan biri substratga [[Kovalent bog'|kovalent]] bog‘langan [[biotin]] teglaridan foydalanishni o‘z ichiga oladi. Agar molekula kerakli [[ligaza]] faolligiga ega bo‘lsa, faol molekulalarni tiklash uchun [[streptavidin]] matritsasidan foydalanish mumkin.

Lincoln va Joyce oldindan sintez qilingan yuqori darajada komplementar oligonukleotidlarni birlashtirish orqali taxminan bir soat ichida o‘z-o‘zini replikatsiya qilishga qodir bo‘lgan ribozim ligazalarini rivojlantirish uchun ''in vitro'' evolyutsiyadan foydalandilar.<ref name="pmid19131595">{{cite journal|vauthors=Lincoln TA, Joyce GF|title=Self-sustained replication of an RNA enzyme|journal=Science|volume=323|issue=5918|pages=1229–1232|date=February 2009|pmid=19131595|pmc=2652413|doi=10.1126/science.1167856|bibcode=2009Sci...323.1229L}}</ref>

Garchi haqiqiy katalizatorlar bo‘lmasa-da, ''aptazimlar'' deb ataladigan sun’iy o‘z-o‘zini qirquvchi [[Ribosvich|ribosvichlarning]] (RNK kalitlari) yaratilishi ham faol tadqiqot sohasi bo‘lib kelmoqda. Ribosvichlar translyatsiyani boshqarish uchun kichik molekula ligandi ta’sirida o‘z tuzilishini o‘zgartiradigan tartibga soluvchi RNK motivlaridir. Ko‘plab metabolitlar va boshqa kichik organik molekulalarni bog‘laydigan ko‘plab tabiiy ribosvichlar ma’lum bo‘lsa-da, ribosvichga asoslangan faqat bitta ribozim tasvirlangan: [[GlmS glyukozamin-6-fosfat faollashtirilgan ribozim|''glmS'']].<ref>{{cite journal|vauthors=Winkler WC, Nahvi A, Roth A, Collins JA, Breaker RR|title=Control of gene expression by a natural metabolite-responsive ribozyme|url=https://archive.org/details/sim_nature-uk_2004-03-18_428_6980/page/n67|journal=Nature|date=March 2004|volume=428|issue=6980|pages=281–286|doi=10.1038/nature02362|pmid=15029187|bibcode=2004Natur.428..281W|s2cid=4301164}}</ref> O‘z-o‘zini qirquvchi ribosvichlarni tavsiflash bo‘yicha dastlabki ishlar ligand sifatida [[Teofillin|teofillindan]] foydalanishga qaratilgan edi. Ushbu tadqiqotlarda [[Ribosoma bog'lanish joyi|ribosoma bog'lanish joyini]] to‘suvchi RNK shpilkasi hosil bo‘ladi va shu bilan translyatsiyani ingibitsiya qiladi. [[Ligand]] ishtirokida (bu holatlarda teofillin) tartibga soluvchi RNK hududi qirqilib, ribosomaning bog‘lanishiga va maqsadli genni translyatsiya qilishiga imkon beradi. Ushbu RNK muhandisligi ishlarining aksariyati yuqoridagi misollardagi kabi yo‘naltirilgan evolyutsiyaga emas, balki oqilona dizayn va oldindan aniqlangan RNK tuzilmalariga asoslangan edi. Keyingi ishlar ribozim ribosvichlarida ishlatiladigan ligandlarni kengaytirib, timin pirofosfatni o‘z ichiga oldi. [[Fluoresentsiya faollashtirilgan hujayra saralash]] ham aptazimlarni loyihalashda ishlatilgan.<ref>{{cite journal|vauthors=Lynch SA, Gallivan JP|title=A flow cytometry-based screen for synthetic riboswitches|journal=Nucleic Acids Research|volume=37|issue=1|pages=184–192|date=January 2009|pmid=19033367|pmc=2615613|doi=10.1093/nar/gkn924}}</ref>

== Qo'llanilishi ==
Ribozimlar [[gen terapiyasi]] orqali kasalliklarni davolash uchun taklif qilingan va ishlab chiqilgan. RNKga asoslangan fermentlardan terapevtik vosita sifatida foydalanishning asosiy qiyinchiliklaridan biri bu organizmdagi katalitik RNK molekulalarining qisqa yarim yemirilish davridir. Bunga qarshi kurashish uchun RNK barqarorligini oshirish maqsadida ribozadagi 2' pozitsiyasi o‘zgartiriladi. Ribozim gen terapiyasining bir yo‘nalishi RNKga asoslangan viruslarni ingibitsiya qilish bo‘lgan.

[[OIV]] (HIV) RNKsiga qarshi qaratilgan ''gen qaychilari'' deb ataladigan sintetik ribozim turi ishlab chiqilgan va OIV infeksiyasi uchun klinik sinovlarga kiritilgan.<ref name="pmid11249628">{{cite journal|vauthors=de Feyter R, Li P|title=Technology evaluation: HIV ribozyme gene therapy, Gene Shears Pty Ltd|journal=Current Opinion in Molecular Therapeutics|volume=2|issue=3|pages=332–335|date=June 2000|pmid=11249628}}</ref><ref name="pmid16426595">{{cite journal|vauthors=Khan AU|title=Ribozyme: a clinical tool|journal=Clinica Chimica Acta; International Journal of Clinical Chemistry|volume=367|issue=1–2|pages=20–27|date=May 2006|pmid=16426595|doi=10.1016/j.cca.2005.11.023}}</ref>

Xuddi shunday, ribozimlar [[gepatit C virusi]] RNKsini, [[SARS koronavirus|SARS koronavirusini]] (SARS-CoV),<ref name=":3">{{cite journal|vauthors=Asha K, Kumar P, Sanicas M, Meseko CA, Khanna M, Kumar B|title=Advancements in Nucleic Acid Based Therapeutics against Respiratory Viral Infections|journal=Journal of Clinical Medicine|volume=8|issue=1|pages=6|date=December 2018|pmid=30577479|pmc=6351902|doi=10.3390/jcm8010006|doi-access=free}}</ref> [[Adenovirus|Adenovirusni]]<ref name=":3" /> hamda [[Gripp A virusi|A]] va [[Gripp B virusi|B gripp virusi]] RNKsini nishonga olish uchun loyihalashtirilgan.<ref>{{cite journal|vauthors=Khanna M, Saxena L, Rajput R, Kumar B, Prasad R|title=Gene silencing: a therapeutic approach to combat influenza virus infections|journal=Future Microbiology|volume=10|issue=1|pages=131–140|date=2015|pmid=25598342|doi=10.2217/fmb.14.94}}</ref><ref>{{cite journal|vauthors=Kumar B, Khanna M, Kumar P, Sood V, Vyas R, Banerjea AC|title=Nucleic acid-mediated cleavage of M1 gene of influenza A virus is significantly augmented by antisense molecules targeted to hybridize close to the cleavage site|journal=Molecular Biotechnology|volume=51|issue=1|pages=27–36|date=May 2012|pmid=21744034|doi=10.1007/s12033-011-9437-z|s2cid=45686564}}</ref><ref>{{cite journal|vauthors=Kumar B, Asha K, Khanna M, Ronsard L, Meseko CA, Sanicas M|title=The emerging influenza virus threat: status and new prospects for its therapy and control|journal=Archives of Virology|volume=163|issue=4|pages=831–844|date=April 2018|pmid=29322273|pmc=7087104|doi=10.1007/s00705-018-3708-y}}</ref><ref name=":3" /> Ribozim virus genomining konservativ hududlarini qirqishga qodir, bu esa sutemizuvchilar hujayra kulturasida virusni kamaytirishi ko‘rsatilgan.<ref>{{cite journal|vauthors=Lieber A, He CY, Polyak SJ, Gretch DR, Barr D, Kay MA|title=Elimination of hepatitis C virus RNA in infected human hepatocytes by adenovirus-mediated expression of ribozymes|url=https://archive.org/details/sim_journal-of-virology_1996-12_70_12/page/8782|journal=Journal of Virology|volume=70|issue=12|pages=8782–8791|date=December 1996|pmid=8971007|pmc=190975|doi=10.1128/JVI.70.12.8782-8791.1996}}</ref> Tadqiqotchilarning ushbu sa’y-harakatlariga qaramay, bu loyihalar klinikadan oldingi bosqichda qolmoqda.

== Ma'lum ribozimlar ==
Yaxshi tasdiqlangan tabiiy ravishda uchraydigan ribozim sinflari:{{div col|colwidth=30em}}
* [[Ribosomal RNK|rRNK]] – Barcha tirik hujayralarda uchraydi va [[oqsil]]larni hosil qilish uchun [[aminokislotalar]]ni bog‘laydi.
* [[GIR1 tarmoqlanuvchi ribozim]]<ref name="pmid16141078">{{cite journal | vauthors = Nielsen H, Westhof E, Johansen S | title = An mRNA is capped by a 2', 5' lariat catalyzed by a group I-like ribozyme | url = https://archive.org/details/sim_science_2005-09-02_309_5740/page/1584 | journal = Science | volume = 309 | issue = 5740 | pages = 1584–1587 | date = September 2005 | pmid = 16141078 | doi = 10.1126/science.1113645 | s2cid = 37002071 | bibcode = 2005Sci...309.1584N }}</ref> – Lariat kepping ribozimi
* [[RNKaza P]] – tRNK molekulalarida RNKning prekursur ketma-ketligini kesib tashlaydi
* [[VS ribozim]] – fosfodiester bog‘ini (qand va fosfat) qirqish
* [[I guruh katalitik intron|I guruh]] o‘z-o‘zini splaysing qiluvchi intron
* [[II guruh intron|II guruh]] o‘z-o‘zini splaysing qiluvchi intron – [[Splaysosoma]], ehtimol, II guruh o‘z-o‘zini splaysing qiluvchi ribozimlardan kelib chiqqan.<ref name="pmid24196718">{{cite journal | vauthors = Fica SM, Tuttle N, Novak T, Li NS, Lu J, Koodathingal P, Dai Q, Staley JP, Piccirilli JA | display-authors = 6 | title = RNA catalyses nuclear pre-mRNA splicing | url = https://archive.org/details/sim_nature-uk_2013-11-14_503_7475/page/228 | journal = Nature | volume = 503 | issue = 7475 | pages = 229–234 | date = November 2013 | pmid = 24196718 | pmc = 4666680 | doi = 10.1038/nature12734 | bibcode = 2013Natur.503..229F }}</ref><ref>{{Cite journal |last1=Xu |first1=Ling |last2=Liu |first2=Tianshuo |last3=Chung |first3=Kevin |last4=Pyle |first4=Anna Marie |date=2023-12-21 |title=Structural insights into intron catalysis and dynamics during splicing |journal=Nature |language=en |volume=624 |issue=7992 |pages=682–688 |doi=10.1038/s41586-023-06746-6 |issn=0028-0836 |pmc=10733145 |pmid=37993708|bibcode=2023Natur.624..682X }}</ref>
* [[Tog'nog'ichsimon ribozim]] – o‘z-o‘zini qirqish va ulanish (ligatsiya) reaksiyalarini katalizlaydi
* [[Bolg'asimon ribozim]] – qaytar qirqish va ligatsiya reaksiyalarini katalizlaydi
* [[Gepatit delta virusi ribozimi|HDV ribozimi]] – o‘z-o‘zini qirqish reaksiyasida RNK transkriptlarini birlik uzunliklarigacha qayta ishlash uchun xizmat qiladi
* [[GlmS glyukozamin-6-fosfat faollashtirilgan ribozim|''glmS'' ribozimi]] – GlcN6P tomonidan faollashganda o‘z-o‘zini qirqish orqali glmS genini tartibga soladi
* [[Tvister ribozim]] – o‘z-o‘zini qirquvchi
* [[Tvister sister ribozim]] – o‘z-o‘zini qirquvchi
* [[Pistolet ribozim]] – o‘z-o‘zini qirquvchi
* [[Bolta ribozim]] – o‘z-o‘zini qirquvchi
* [[Viroidlar]] oqsil qobig‘iga ega bo‘lmagan infeksion halqasimon RNKlar.{{div col end}}

== Yana qarang ==
{{div col|colwidth=30em}}
*[[Dezoksiribozim]]
*[[Spiegelman yirtqichi]]
*[[Kataliz]]
*[[Ferment]]
*[[RNK dunyosi nazariyasi]]
*[[Peptid nuklein kislotasi]]
*[[Nuklein kislota analoglari]]
*[[PAU dunyosi nazariyasi]]
*[[Ligandlarning eksponensial boyitilishi orqali tizimli evolyutsiyasi|SELEX]]
*[[OLE RNK]]
{{div col end}}

== Izohlar va adabiyotlar ==
{{reflist}}

== Qo'shimcha o'qish uchun ==
{{refbegin|33em}}
* {{cite book |year=2011 |title=Structural and catalytic roles of metal ions in RNA |publisher=RSC Publishing |pages=vii–ix |doi=10.1039/9781849732512 |isbn=978-1-84973-251-2 |vauthors=Sigel A, Sigel H, Sigel RK |editor-first1=Astrid |editor-first2=Helmut |editor-first3=Roland K O |editor-first4=Astrid |editor-first5=Helmut |editor-first6=Roland K O |editor-first7=Astrid |editor-first8=Helmut |editor-first9=Roland K O |editor-first10=Astrid |editor-first11=Helmut |editor-first12=Roland K O |editor-last1=Sigel |editor-last2=Sigel |editor-last3=Sigel |editor-last4=Sigel |editor-last5=Sigel |editor-last6=Sigel |editor-last7=Sigel |editor-last8=Sigel |editor-last9=Sigel |editor-last10=Sigel |editor-last11=Sigel |editor-last12=Sigel |journal=Metal Ions in Life Sciences |volume=9 |pmid=22010266}}
* {{cite book |year=2011 |chapter=Metal ions: supporting actors in the playbook of small ribozymes |title=Structural and Catalytic Roles of Metal Ions in RNA |pages=175–96 |doi=10.1039/9781849732512-00175 |isbn=978-1-84973-094-5 |vauthors=Johnson-Buck AE, McDowell SE, Walter NG |journal=Metal Ions in Life Sciences |volume=9 |pmid=22010272 |pmc=3365584}}
* {{cite book |year=2011 |chapter=Multiple roles of metal ions in large ribozymes |title=Structural and Catalytic Roles of Metal Ions in RNA |pages=197–234 |doi=10.1039/9781849732512-00197 |isbn=978-1-84973-094-5 |vauthors=Donghi D, Schnabl J |journal=Metal Ions in Life Sciences |volume=9 |pmid=22010273}}
* {{cite book |year=2011 |chapter=The ribosome: a molecular machine powered by RNA |title=Structural and Catalytic Roles of Metal Ions in RNA |pages=253–75 |doi=10.1039/9781849732512-00253 |isbn=978-1-84973-094-5 |vauthors=Trappl K, Polacek N |journal=Metal Ions in Life Sciences |volume=9 |pmid=22010275}}
* {{cite book |year=2011 |chapter=Metal ion requirements in artificial ribozymes that catalyze aminoacylation and redox reactions |title=Structural and Catalytic Roles of Metal Ions in RNA |pages=277–97 |doi=10.1039/9781849732512-00277 |isbn=978-1-84973-094-5 |vauthors=Suga H, Futai K, Jin K |journal=Metal Ions in Life Sciences |volume=9 |pmid=22010276}}
* {{cite book |year=2011 |chapter=Metal ion binding and function in natural and artificial small RNA enzymes from a structural perspective |title=Structural and Catalytic Roles of Metal Ions in RNA |pages=299–345 |doi=10.1039/9781849732512-00299 |isbn=978-1-84973-094-5 |vauthors=Wedekind JE |journal=Metal Ions in Life Sciences |volume=9 |pmid=22010277}}
* {{cite journal|vauthors=Doherty EA, Doudna JA|title=Ribozyme structures and mechanisms|journal=Annual Review of Biophysics and Biomolecular Structure|volume=30|pages=457–475|year=2001|pmid=11441810|doi=10.1146/annurev.biophys.30.1.457}}
* {{cite journal|vauthors=Joyce GF|title=Directed evolution of nucleic acid enzymes|url=https://archive.org/details/sim_annual-review-of-biochemistry_2004_73/page/790|journal=Annual Review of Biochemistry|volume=73|pages=791–836|year=2004|pmid=15189159|doi=10.1146/annurev.biochem.73.011303.073717}}
* {{cite journal|vauthors=Ikawa Y, Tsuda K, Matsumura S, Inoue T|title=De novo synthesis and development of an RNA enzyme|journal=Proceedings of the National Academy of Sciences of the United States of America|volume=101|issue=38|pages=13750–13755|date=September 2004|pmid=15365187|pmc=518828|doi=10.1073/pnas.0405886101|doi-access=free|bibcode=2004PNAS..10113750I}}
{{refend}}

== Havolalar ==

* [https://www.ibiology.org/genetics-and-gene-regulation/discovering-ribozymes/ Tom Cech's Short Talk: "Discovering Ribozymes"]
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