来自哈佛-麻省的白头研究所，麻省理工学院，哈佛大学医学院的生物学系，Koch高级癌症研究中心等处的研究者发现了一类大型的非编码RNA，这些RNA的特性揭示来哺乳动物基因组的又一重大发现。该研究成果发表在2月1日的Nature在线版上。
该研究发现了一类新型的“大型插入性非编码RNA”（large intervening non-coding RNA，简称，lincRNAs），研究者发现lincRNAs对生命体的健康以及疾病都具有重要的影响意义，其中包括，对癌症，免疫信号和干细胞生物学特性都具有影响意义。
据白头研究所的主管，Eric Lander介绍，我们一直清楚，人类基因组秘密有待人们探索，但是令人意外的是，竟然有类如此大型的编码non-coding RNA的基因被我们错失，知道现在才被发现。
以前经典的基因组学理论认为，人类和小鼠的基因组可编码大型的RNA分子，这些大型的RNA在进化上并不属于保守型，由于多变，科学家们认为这些大型的RNA分子并没有生物学功能，将其比喻为只是基因组上的“噪音”（genomic noise）。然而，新发现的lincRNAs（1000多种）却是一种进化上保守的RNA分子，并且最令人惊讶的是它还具有多种生物功能。
科学家们用细胞技术检测出100多个lincRNAs的生物学功能，尤其值得关注的是，有些lincRNA还是调节转录的关键影响因子，比如说，p53，NKkB，Sox2，Oct4（也称Pou5f1）和Nanog。
这些研究结果表明，lincRNAs不仅对胚胎干细胞的多能性的维持具有重要的意义，对细胞增殖作用也具有重大的影响作用，它参与多种生物功能，具有重大的意义。
这无疑是非编码RNA（non-coding RNA）研究的一大重大发现。（生物谷Bioon.com）
生物谷推荐原始出处：
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.
