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

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

Author information

1
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.
2
St. Laurent Institute, 317 New Boston St., Suite 201, Woburn, MA 01801, USA AcademGene Ltd., 6, Acad. Lavrentjev ave., Novosibirsk 630090, Russia.
3
AcademGene Ltd., 6, Acad. Lavrentjev ave., Novosibirsk 630090, Russia State Research Center of Virology and Biotechnology 'Vector', Novosibirsk, Russia A. P. Ershov Institute of Informatics Systems SB RAS, 6, Acad. Lavrentjev ave., Novosibirsk 630090, Russia.
4
Institute of Genomics, School of Biomedical Sciences, Huaqiao University, 668 Jimei Road, Xiamen 361021, China.
5
St. Laurent Institute, 317 New Boston St., Suite 201, Woburn, MA 01801, USA AcademGene Ltd., 6, Acad. Lavrentjev ave., Novosibirsk 630090, Russia Federal Research Center Institute of Cytology and Genetics SB RAS, 10, Acad. Lavrentjev ave., Novosibirsk 630090, Russia.
6
St. Laurent Institute, 317 New Boston St., Suite 201, Woburn, MA 01801, USA AcademGene Ltd., 6, Acad. Lavrentjev ave., Novosibirsk 630090, Russia A. P. Ershov Institute of Informatics Systems SB RAS, 6, Acad. Lavrentjev ave., Novosibirsk 630090, Russia.
7
RIKEN Omics Science Center (OSC), 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, 230-0045, Japan RIKEN Center for Life Science Technologies, Division of Genomic Technologies, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa, 230-0045, Japan.
8
RIKEN Omics Science Center (OSC), 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, 230-0045, Japan RIKEN Center for Life Science Technologies, Division of Genomic Technologies, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa, 230-0045, Japan RIKEN Preventive Medicine and Diagnosis Innovation Program (PMI), 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan.
9
RIKEN Omics Science Center (OSC), 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, 230-0045, Japan RIKEN Center for Life Science Technologies, Division of Genomic Technologies, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa, 230-0045, Japan Telethon Kids Institute, The University of Western Australia, 100 Roberts Road, Subiaco, Subiaco, 6008, Western Australia, Australia.
10
LBCMCP, Centre de Biologie Intégrative (CBI), Université de Toulouse, CNRS, UPS, France.
11
The George Washington University Medical Center, Department of Medicine, Division of Genomic Medicine, 2300 I St. NW, Washington, DC, USA.
12
RIKEN Omics Science Center (OSC), 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, 230-0045, Japan RIKEN Preventive Medicine and Diagnosis Innovation Program (PMI), 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan.
13
Center for Therapeutic Innovation and Department of Psychiatry and Behavioral Sciences, University of Miami Miller School of Medicine, 1501 NW 10th Ave., Miami, FL 33136, USA clawah@gmail.com.
14
Institute of Genomics, School of Biomedical Sciences, Huaqiao University, 668 Jimei Road, Xiamen 361021, China St. Laurent Institute, 317 New Boston St., Suite 201, Woburn, MA 01801, USA philippk08@hotmail.com.

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.

PMID:
27001520
PMCID:
PMC4838384
DOI:
10.1093/nar/gkw162
[Indexed for MEDLINE]
Free PMC Article

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