日本RIKEN高级科学研究所分子和细胞生物学实验室,东京大学研究生院生命科学院,麻省波士顿学院生物学系,京都大学研究生医学院遗传学系的科学家发现非编码RNAs的级联转录过程是改变染色质的过程。相关的成果公布在11月6日出版的Nature期刊上。
最近采用高通量的tilling arrays技术对转录子开展大规模的研究,并对整个cDNA文库进行分析(FANTOM3 consortium),分析结果表明,大部分的转录产物都是非编码RNAs(non-codingRNAs,ncRNA)。对这些转录子进行分析发现这些先前认为没有功能的RNA其实是转录的活性区域,具有多种转录活性特征。并且,研究发现大部分的长片段(上千kb)实际上是转录mRNA的活性位点。目前,绝大多数的ncRNA的功能都不为人所知,甚至有多种争论,人们对它的功能意见不一。
研究者对裂殖酵母在转录期间位于fbp1+转座子区域的RNA聚合酶II的ncRNA进行研究。结果发现染色质fbp1+区域日益变成一个开放性的构型,几种不同的ncRNAs都由这一区域转录而来。这些ncRNA与RNAPII在fbp1+转录起点的上游区域一一配对。如果在上游区域插入一个转录终止子,将导致ncRNA转录停止,染色质停止改变。
研究者的结论是,转录的过程是要促进DNA序列接近转录激活因子和RNAPII的过程。(生物谷Bioon.com)
生物谷推荐原始出处:
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.