據(jù)外媒8月10日?qǐng)?bào)道,研究人員近日利用一種量化單分子測(cè)序技術(shù),探測(cè)到人類(lèi)細(xì)胞中一類(lèi)新型MicroRNA,在基因轉(zhuǎn)錄方面代表著一個(gè)全新的種類(lèi),并證實(shí)了長(zhǎng)久以來(lái)的一種假設(shè),,哺乳動(dòng)物細(xì)胞能通過(guò)直接復(fù)制RNA分子來(lái)合成RNA。這一研究由美國(guó)匹茲堡大學(xué)醫(yī)學(xué)院,、瑞士日內(nèi)瓦大學(xué)醫(yī)學(xué)院和兩家生物科技公司共同進(jìn)行,,相關(guān)論文發(fā)表在最新一期《自然》(Nature)雜志上。
這是首次證明人類(lèi)細(xì)胞能像復(fù)制DNA一樣復(fù)制RNA,。匹茲堡大學(xué)醫(yī)學(xué)院計(jì)算與系統(tǒng)生物學(xué)教授,、論文合著者比諾·約翰博士表示,該發(fā)現(xiàn)強(qiáng)調(diào)了人類(lèi)細(xì)胞中RNA群體的多樣性,,這些新型RNA對(duì)于開(kāi)拓治療新路徑,,尤其對(duì)診斷學(xué)的發(fā)展有重要意義。
長(zhǎng)期以來(lái)科學(xué)家們認(rèn)為,,人類(lèi)細(xì)胞中的所有RNA都從DNA模版復(fù)制,,以往的記錄顯示,這次新觀察到的從RNA到RNA的復(fù)制機(jī)制,,只存在于植物和簡(jiǎn)單的有機(jī)物如酵母菌中,,與一種名為RNA依賴(lài)性RNA聚合酶(簡(jiǎn)稱(chēng)RdRP)有關(guān),這種酶參與關(guān)鍵性細(xì)胞調(diào)控程序,。
這次研究發(fā)現(xiàn),,人類(lèi)細(xì)胞中有數(shù)千種能直接復(fù)制的MicroRNA,而此前這些RNA卻未被重視,。在對(duì)人類(lèi)細(xì)胞和組織中的這些MicroRNA進(jìn)行整理歸類(lèi)中,,研究人員還發(fā)現(xiàn)了一些RNA的新種類(lèi),包括抗轉(zhuǎn)錄的相關(guān)短鏈RNA,,它可能是從信使RNA中分離出來(lái)的一種未明確的蛋白質(zhì)編碼基因,,其RNA復(fù)制機(jī)制在人類(lèi)癌細(xì)胞戰(zhàn)線(xiàn)上無(wú)處不在。
這種未編碼RNA分子一直被忽視,,只因?yàn)橐郧暗臏y(cè)序平臺(tái)很難提供精確的量化測(cè)定,。其中一家生物科技公司首席科技官帕德里克·米羅斯博士認(rèn)為,單分子測(cè)序在精確廣泛的基因程序分析方面具有重要作用,,也給臨床應(yīng)用提供了便利,。(常麗君)(生物谷Bioon.com)
Science:可調(diào)節(jié)膽固醇動(dòng)態(tài)平衡的MicroRNA
NEJM:microRNA表達(dá)影響肝癌復(fù)發(fā)
Cell:哺乳動(dòng)物microRNA表達(dá)圖譜
PNAS:microRNA或可成為早期癌癥檢測(cè)生物標(biāo)記
Nature:microRNA最初形成時(shí)的作用
生物谷推薦原文出處:
Nature doi:10.1038/nature09190
New class of gene-termini-associated human RNAs suggests a novel RNA copying mechanism
Philipp Kapranov1,6, Fatih Ozsolak1,6, Sang Woo Kim2,6, Sylvain Foissac3,6, Doron Lipson1, Chris Hart1, Steve Roels1, Christelle Borel4, Stylianos E. Antonarakis4, A. Paula Monaghan5, Bino John2 & Patrice M. Milos1
Helicos BioSciences Corporation, 1 Kendall Sq. Ste B7301 Cambridge, Massachusetts 02139-1671, USA
Department of Computational and Systems Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15260, USA
Integromics, S.L., Grisolía 2, 28760 Tres Cantos, Madrid, Spain
Department of Genetic Medicine and Development, University of Geneva Medical School, University of Geneva, 1 rue Michel-Servet, 1211 Geneva, Switzerland
Department of Neurobiology, University of Pittsburgh, 3501 Fifth Avenue, Pittsburgh, Pennsylvania 15260, USA
These authors contributed equally to this work.
Small (<200 nucleotide) RNA (sRNA) profiling of human cells using various technologies demonstrates unexpected complexity of sRNAs with hundreds of thousands of sRNA species present1, 2, 3, 4. Genetic and in vitro studies show that these RNAs are not merely degradation products of longer transcripts but could indeed have a function1, 2, 5. Furthermore, profiling of RNAs, including the sRNAs, can reveal not only novel transcripts, but also make clear predictions about the existence and properties of novel biochemical pathways operating in a cell. For example, sRNA profiling in human cells indicated the existence of an unknown capping mechanism operating on cleaved RNA2, a biochemical component of which was later identified6. Here we show that human cells contain a novel type of sRNA that has non-genomically encoded 5′ poly(U) tails. The presence of these RNAs at the termini of genes, specifically at the very 3′ ends of known mRNAs, strongly argues for the presence of a yet uncharacterized endogenous biochemical pathway in cells that can copy RNA. We show that this pathway can operate on multiple genes, with specific enrichment towards transcript-encoding components of the translational machinery. Finally, we show that genes are also flanked by sense, 3′ polyadenylated sRNAs that are likely to be capped.