Comprehensive characterization of 10,571 mouse large intergenic noncoding RNAs from whole transcriptome sequencing

PLoS One. 2013 Aug 12;8(8):e70835. doi: 10.1371/journal.pone.0070835. eCollection 2013.

Abstract

Large intergenic noncoding RNAs (lincRNAs) have been recognized in recent years to constitute a significant portion of the mammalian transcriptome, yet their biological functions remain largely elusive. This is partly due to an incomplete annotation of tissue-specific lincRNAs in essential model organisms, particularly in mice, which has hindered the genetic annotation and functional characterization of these novel transcripts. In this report, we performed ab initio assembly of 1.9 billion tissue-specific RNA-sequencing reads across six tissue types, and identified 3,965 novel expressed lincRNAs in mice. Combining these with 6,606 documented lincRNAs, we established a comprehensive catalog of 10,571 transcribed lincRNAs. We then systemically analyzed all mouse lincRNAs to reveal that some of them are evolutionally conserved and that they exhibit striking tissue-specific expression patterns. We also discovered that mouse lincRNAs carry unique genomic signatures, and that their expression level is correlated with that of neighboring protein-coding transcripts. Finally, we predicted that a large portion of tissue-specific lincRNAs are functionally associated with essential biological processes including the cell cycle and cell development, and that they could play a key role in regulating tissue development and functionality. Our analyses provide a framework for continued discovery and annotation of tissue-specific lincRNAs in model organisms, and our transcribed mouse lincRNA catalog will serve as a roadmap for functional analyses of lincRNAs in genetic mouse models.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cluster Analysis
  • Evolution, Molecular
  • Gene Expression Profiling*
  • Gene Expression Regulation
  • Mice
  • Open Reading Frames
  • Organ Specificity / genetics
  • RNA, Long Noncoding / genetics*
  • Sequence Analysis, RNA
  • Transcription Initiation Site
  • Transcriptional Activation
  • Transcriptome*

Substances

  • RNA, Long Noncoding

Grants and funding

This work was supported by a grant from the National High Technology Research and Development Program of China (863 Program) (No. 2012AA022501); Ping Li and Haiming Cao are funded by the Division of Intramural Research of the National Heart Lung and Blood Institute (HL006103-02) of the NIH, USA. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.