來自哈佛-麻省的白頭研究所，麻省理工學院,，哈佛大學醫(yī)學院的生物學系,，Koch高級癌癥研究中心等處的研究者發(fā)現(xiàn)了一類大型的非編碼RNA，這些RNA的特性揭示來哺乳動物基因組的又一重大發(fā)現(xiàn),。該研究成果發(fā)表在2月1日的Nature在線版上,。
該研究發(fā)現(xiàn)了一類新型的“大型插入性非編碼RNA”（large intervening non-coding RNA，簡稱,，lincRNAs）,，研究者發(fā)現(xiàn)lincRNAs對生命體的健康以及疾病都具有重要的影響意義,，其中包括，對癌癥,，免疫信號和干細胞生物學特性都具有影響意義,。
據(jù)白頭研究所的主管，Eric Lander介紹,，我們一直清楚,，人類基因組秘密有待人們探索，但是令人意外的是,，竟然有類如此大型的編碼non-coding RNA的基因被我們錯失,，知道現(xiàn)在才被發(fā)現(xiàn)。
以前經(jīng)典的基因組學理論認為,，人類和小鼠的基因組可編碼大型的RNA分子,，這些大型的RNA在進化上并不屬于保守型，由于多變,，科學家們認為這些大型的RNA分子并沒有生物學功能,，將其比喻為只是基因組上的“噪音”（genomic noise）。然而,，新發(fā)現(xiàn)的lincRNAs（1000多種）卻是一種進化上保守的RNA分子,，并且最令人驚訝的是它還具有多種生物功能。
科學家們用細胞技術檢測出100多個lincRNAs的生物學功能,，尤其值得關注的是,，有些lincRNA還是調(diào)節(jié)轉錄的關鍵影響因子，比如說,，p53,，NKkB，Sox2,，Oct4（也稱Pou5f1）和Nanog,。
這些研究結果表明，lincRNAs不僅對胚胎干細胞的多能性的維持具有重要的意義,，對細胞增殖作用也具有重大的影響作用,，它參與多種生物功能,，具有重大的意義,。
這無疑是非編碼RNA（non-coding RNA）研究的一大重大發(fā)現(xiàn)。（生物谷Bioon.com）
生物谷推薦原始出處：
Nature advance online publication 1 February 2009 | doi:10.1038/nature07672
Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals
Mitchell Guttman1,2, Ido Amit1, Manuel Garber1, Courtney French1, Michael F. Lin1, David Feldser3, Maite Huarte1,6, Or Zuk1, Bryce W. Carey2,8, John P. Cassady2,8, Moran N. Cabili7, Rudolf Jaenisch2,8, Tarjei S. Mikkelsen1,4, Tyler Jacks2,3, Nir Hacohen1,9, Bradley E. Bernstein1,10,11, Manolis Kellis1,5, Aviv Regev1,2, John L. Rinn1,6,11,12 & Eric S. Lander1,2,7,8,12
1 Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA
2 Department of Biology,
3 The Koch Institute for Integrative Cancer Research,
4 Division of Health Sciences and Technology, and,
5 Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
6 Department of Pathology, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA
7 Department of Systems Biology, Harvard Medical School, Boston, Massachusetts 02114, USA
8 Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA
9 Center for Immunology and Inflammatory Diseases,
10 Molecular Pathology Unit and Center for Cancer Research, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA
11 Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA
12 These authors contributed equally to this work.
There is growing recognition that mammalian cells produce many thousands of large intergenic transcripts1, 2, 3, 4. However, the functional significance of these transcripts has been particularly controversial. Although there are some well-characterized examples, most (>95%) show little evidence of evolutionary conservation and have been suggested to represent transcriptional noise5, 6. Here we report a new approach to identifying large non-coding RNAs using chromatin-state maps to discover discrete transcriptional units intervening known protein-coding loci. Our approach identified 1,600 large multi-exonic RNAs across four mouse cell types. In sharp contrast to previous collections, these large intervening non-coding RNAs (lincRNAs) show strong purifying selection in their genomic loci, exonic sequences and promoter regions, with greater than 95% showing clear evolutionary conservation. We also developed a functional genomics approach that assigns putative functions to each lincRNA, demonstrating a diverse range of roles for lincRNAs in processes from embryonic stem cell pluripotency to cell proliferation. We obtained independent functional validation for the predictions for over 100 lincRNAs, using cell-based assays. In particular, we demonstrate that specific lincRNAs are transcriptionally regulated by key transcription factors in these processes such as p53, NFB, Sox2, Oct4 (also known as Pou5f1) and Nanog. Together, these results define a unique collection of functional lincRNAs that are highly conserved and implicated in diverse biological processes.
