日本RIKEN高級科學(xué)研究所分子和細(xì)胞生物學(xué)實(shí)驗(yàn)室,,東京大學(xué)研究生院生命科學(xué)院,,麻省波士頓學(xué)院生物學(xué)系,,京都大學(xué)研究生醫(yī)學(xué)院遺傳學(xué)系的科學(xué)家發(fā)現(xiàn)非編碼RNAs的級聯(lián)轉(zhuǎn)錄過程是改變?nèi)旧|(zhì)的過程,。相關(guān)的成果公布在11月6日出版的Nature期刊上,。
最近采用高通量的tilling arrays技術(shù)對轉(zhuǎn)錄子開展大規(guī)模的研究,,并對整個cDNA文庫進(jìn)行分析(FANTOM3 consortium),分析結(jié)果表明,,大部分的轉(zhuǎn)錄產(chǎn)物都是非編碼RNAs(non-codingRNAs,,ncRNA),。對這些轉(zhuǎn)錄子進(jìn)行分析發(fā)現(xiàn)這些先前認(rèn)為沒有功能的RNA其實(shí)是轉(zhuǎn)錄的活性區(qū)域,具有多種轉(zhuǎn)錄活性特征,。并且,,研究發(fā)現(xiàn)大部分的長片段(上千kb)實(shí)際上是轉(zhuǎn)錄mRNA的活性位點(diǎn)。目前,,絕大多數(shù)的ncRNA的功能都不為人所知,,甚至有多種爭論,人們對它的功能意見不一,。
研究者對裂殖酵母在轉(zhuǎn)錄期間位于fbp1+轉(zhuǎn)座子區(qū)域的RNA聚合酶II的ncRNA進(jìn)行研究,。結(jié)果發(fā)現(xiàn)染色質(zhì)fbp1+區(qū)域日益變成一個開放性的構(gòu)型,幾種不同的ncRNAs都由這一區(qū)域轉(zhuǎn)錄而來,。這些ncRNA與RNAPII在fbp1+轉(zhuǎn)錄起點(diǎn)的上游區(qū)域一一配對,。如果在上游區(qū)域插入一個轉(zhuǎn)錄終止子,將導(dǎo)致ncRNA轉(zhuǎn)錄停止,,染色質(zhì)停止改變,。
研究者的結(jié)論是,轉(zhuǎn)錄的過程是要促進(jìn)DNA序列接近轉(zhuǎn)錄激活因子和RNAPII的過程,。(生物谷Bioon.com)
生物谷推薦原始出處:
Nature 456, 130-134 (6 November 2008) | doi:10.1038/nature07348
Stepwise chromatin remodelling by a cascade of transcription initiation of non-coding RNAs
Kouji Hirota1,2,4, Tomoichiro Miyoshi2, Kazuto Kugou1,2, Charles S. Hoffman3, Takehiko Shibata1 & Kunihiro Ohta1,2
1 Cellular & Molecular Biology Laboratory, RIKEN Advanced Science Institute, Wako-shi, Saitama 351-0198, Japan
2 Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, Komaba 3-8-1, Meguro-ku, Tokyo 153-8902, Japan
3 Biology Department, Boston College, Chestnut Hill, Massachusetts 02467, USA
4 Present address: Department of Radiation Genetics, Kyoto University Graduate School of Medicine, Yoshida Konoe, Sakyo-ku, Kyoto 606-8501, Japan.
Recent transcriptome analyses using high-density tiling arrays1, 2, 3 and data from large-scale analyses of full-length complementary DNA libraries by the FANTOM3 consortium4, 5 demonstrate that many transcripts are non-coding RNAs (ncRNAs). These transcriptome analyses indicate that many of the non-coding regions, previously thought to be functionally inert, are actually transcriptionally active regions with various features. Furthermore, most relatively large (several kilobases) polyadenylated messenger RNA transcripts are transcribed from regions harbouring little coding potential. However, the function of such ncRNAs is mostly unknown and has been a matter of debate2. Here we show that RNA polymerase II (RNAPII) transcription of ncRNAs is required for chromatin remodelling at the fission yeast Schizosaccharomyces pombe fbp1 + locus during transcriptional activation. The chromatin at fbp1 + is progressively converted to an open configuration, as several species of ncRNAs are transcribed through fbp1 +. This is coupled with the translocation of RNAPII through the region upstream of the eventual fbp1 + transcriptional start site. Insertion of a transcription terminator into this upstream region abolishes both the cascade of transcription of ncRNAs and the progressive chromatin alteration. Our results demonstrate that transcription through the promoter region is required to make DNA sequences accessible to transcriptional activators and to RNAPII.