Mikro RNK

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Prikaz interakcije miRNA i iRNK

MikroRNK ili mikro RNK (skraćeno miRNK, eng. microRNA, miRNA) je mala nekodirajuća molekula RNK, od oko 22 nukleotida, koja je nađena kod biljaka, životinja i nekih virusa. Njena je RNK prigušena u posttranskripcijskom reguliranju ekspresije gena.[1][2][3][4][5][6]

Kod eukariota je kodirana iz jedarne DNK, kao kod svih organizama čiji je genom zasnovan na DNK. Uloga miRNK se ostvaruje preko baznog uparivanja s komplementarnim sekvencama unutar molekule iRNK.[7] Kao rezultat toga, ove su molekule iRNK su prigušene jednim ili više od sljedećih procesa:

Primjeri miRNK matične petlje sa zrelom miRNK (crveno)

Genom čovjeka može kodirati preko 1.000 miRNK,[9][10] koje su učestale u mnogim tipovima sisarskih ćelija,[11][12] a javljaju se za kopiranje oko 60% gena čovjeka i ostalih sisara.[13][14]

Ove, miRNK su dobro konzervirane sekvence i kod biljaka i kod životinja, a snatra se da su vitalnog značaja i evolucijski drevne komponente regulacije gena.[15][16][17][18][19] Iako su osnovne komponente mikroRNK puta među biljkama i životinjama konzervirane, čini se da se miRNK repertoar u dva kraljevstva samostalno pojavio sa različitim primarnim načinom djelovanja.[20][21] Biljne miRNK obično imaju približno perfektno uparivanje sa odgovarajućim iRNK ciljnim molekulama, koje izazivaju represiju gena tokom prerade ciljnih transkripata.[22] Nasuprot tome, životinjske miRNK su sposobne za prepoznavanje njihovih ciljnih iRNK pomoću 6–8 nukleotida na 5' kraju miRNK,[13][23][24] koje nisu dovoljno uparene da induciraju cijepanje ciljnih iRNK.[7] Kod životinja je obilježavajuća kombinirana regulacija miRNK.[7][25]

Data miRNK može imati na stotine različitih ciljnih iRNK, a dati cilj može biti reguliran multiplim miRNK-a.[14][26]

Historija[uredi | uredi izvor]

Prva miRNK je otkrivena ranih 1990-ih.[27][28] Međutim, miRNK nije bila prepoznata kao posebna klasa bioloških regulatora sve do ranih 2000-tih.[29][30][31][32][33] Tako je istraživanje pokazalo da se u različitim tkivima jispoljavaju n različiti setovi miRNK,[12][34] kao i njihove multiple uloge u razvoju biljaka i životinja, u mnogim ostalim biološkim procesim.[22][35][36][37][38][39][40] Aberantna ekspresija miRNK uvjetuje razna bolesna stanja. U toku je istraživanje miRNK-baziranih terapija.[41][42][43][44]

Procjena prosječnog broja informacijskih RNK koje su ciljevi represije putem tipskih miRNK varira, ovisno o metodu,[45] ali mnogi pristupi pokazuju da sisarske miRNK mogu imati mnoge pojedinačne ciljeve. Naprimjer, jedna analiza visoko konzerviranih miRNK kod kičmenjaka pokazuje da svaka ima prosječno oko 400 konserviranih ciljeva.[14] Slično tome, eksperimenti su pokazali da jedna miRNK može reducirati stabilnost stotina pojedinačnih molekula informacijske RNK.[46] Other experiments show that a single miRNA may repress the production of hundreds of proteins, but that this repression often is relatively mild (less than 2-fold).[47][48]

Prva ljudska bolest koja je sa poremećajem regulacije miRNA bila je hronična limfocitna leukemija. Sljedili su ostali malgniteti B ćelija.[49]

Sekundarna struktura djetelinaste petlje obavljena je sljedeće X_zračnom kristalografijom u dvije nezavisne istraživačke grupe, 197. Pored toga otkrivena je ribosomska RNK , a zatim URNA u ranim 1980-im. Od tada, nastavlja se otkrivanje novih nekodirajućih RNK: snoRNAs, Xist, CRISPR i još mnogih. Nedavni značajni dodaci uključuju riboswitche i miRNK, te otkriće RNK mehanizma. Zajedno sa saradnicima, Craig C. Mello i Andrew Fire su 2006. Dobuili Nobelovu nagradu za fiziologijui ili medicinu.[50][51]

Također pogledajte[uredi | uredi izvor]

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