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使用系统生物学方法对非编码RNA的vlinc类别进行功能注释。

Functional annotation of the vlinc class of non-coding RNAs using systems biology approach.

作者信息

St Laurent Georges, Vyatkin Yuri, Antonets Denis, Ri Maxim, Qi Yao, Saik Olga, Shtokalo Dmitry, de Hoon Michiel J L, Kawaji Hideya, Itoh Masayoshi, Lassmann Timo, Arner Erik, Forrest Alistair R R, Nicolas Estelle, McCaffrey Timothy A, Carninci Piero, Hayashizaki Yoshihide, Wahlestedt Claes, Kapranov Philipp

机构信息

St. Laurent Institute, 317 New Boston St., Suite 201, Woburn, MA 01801, USA Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, RI, USA.

St. Laurent Institute, 317 New Boston St., Suite 201, Woburn, MA 01801, USA AcademGene Ltd., 6, Acad. Lavrentjev ave., Novosibirsk 630090, Russia.

出版信息

Nucleic Acids Res. 2016 Apr 20;44(7):3233-52. doi: 10.1093/nar/gkw162. Epub 2016 Mar 21.

Abstract

Functionality of the non-coding transcripts encoded by the human genome is the coveted goal of the modern genomics research. While commonly relied on the classical methods of forward genetics, integration of different genomics datasets in a global Systems Biology fashion presents a more productive avenue of achieving this very complex aim. Here we report application of a Systems Biology-based approach to dissect functionality of a newly identified vast class of very long intergenic non-coding (vlinc) RNAs. Using highly quantitative FANTOM5 CAGE dataset, we show that these RNAs could be grouped into 1542 novel human genes based on analysis of insulators that we show here indeed function as genomic barrier elements. We show that vlinc RNAs genes likely function in cisto activate nearby genes. This effect while most pronounced in closely spaced vlinc RNA-gene pairs can be detected over relatively large genomic distances. Furthermore, we identified 101 vlinc RNA genes likely involved in early embryogenesis based on patterns of their expression and regulation. We also found another 109 such genes potentially involved in cellular functions also happening at early stages of development such as proliferation, migration and apoptosis. Overall, we show that Systems Biology-based methods have great promise for functional annotation of non-coding RNAs.

摘要

人类基因组编码的非编码转录本的功能是现代基因组学研究梦寐以求的目标。虽然通常依赖正向遗传学的经典方法,但以全球系统生物学方式整合不同的基因组数据集为实现这一非常复杂的目标提供了一条更有效的途径。在此,我们报告了一种基于系统生物学的方法在剖析新发现的一大类非常长的基因间非编码(vlinc)RNA功能方面的应用。利用高度定量的FANTOM5 CAGE数据集,我们表明,基于对绝缘子的分析,这些RNA可被归为1542个新的人类基因,我们在此证明这些绝缘子确实起到基因组屏障元件的作用。我们表明,vlinc RNA基因可能在顺式作用中激活附近的基因。这种效应在紧密间隔的vlinc RNA-基因对中最为明显,但在相对较大的基因组距离上也能检测到。此外,基于其表达和调控模式,我们鉴定出101个可能参与早期胚胎发生的vlinc RNA基因。我们还发现另外109个这样的基因可能参与发育早期也会发生的细胞功能,如增殖、迁移和凋亡。总体而言,我们表明基于系统生物学的方法在非编码RNA的功能注释方面具有很大的前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52a6/4838384/6d4a27692f23/gkw162fig1.jpg

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