Genome-wide analysis of long noncoding RNA stability

Clark, Michael B., Johnston, Rebecca L., Inostroza-Ponta, Mario, Fox, Archa H., Fortini, Ellen, Moscato, Pablo, Dinger, Marcel E. and Mattick, John S. (2012) Genome-wide analysis of long noncoding RNA stability. Genome Research, 22 5: 885-898. doi:10.1101/gr.131037.111

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Author Clark, Michael B.
Johnston, Rebecca L.
Inostroza-Ponta, Mario
Fox, Archa H.
Fortini, Ellen
Moscato, Pablo
Dinger, Marcel E.
Mattick, John S.
Title Genome-wide analysis of long noncoding RNA stability
Journal name Genome Research   Check publisher's open access policy
ISSN 1088-9051
1549-5469
Publication date 2012-05-01
Sub-type Article (original research)
DOI 10.1101/gr.131037.111
Open Access Status File (Publisher version)
Volume 22
Issue 5
Start page 885
End page 898
Total pages 14
Place of publication Cold Spring Harbor, NY, United States
Publisher Cold Spring Harbor Laboratory Press
Collection year 2013
Language eng
Formatted abstract
Transcriptomic analyses have identified tens of thousands of intergenic, intronic, and cis-antisense long noncoding RNAs (lncRNAs) that are expressed from mammalian genomes. Despite progress in functional characterization, little is known about the post-transcriptional regulation of lncRNAs and their half-lives. Although many are easily detectable by a variety of techniques, it has been assumed that lncRNAs are generally unstable, but this has not been examined genome-wide. Utilizing a custom noncoding RNA array, we determined the half-lives of ∼800 lncRNAs and ∼12,000 mRNAs in the mouse Neuro-2a cell line. We find only a minority of lncRNAs are unstable. LncRNA half-lives vary over a wide range, comparable to, although on average less than, that of mRNAs, suggestive of complex metabolism and widespread functionality. Combining half-lives with comprehensive lncRNA annotations identified hundreds of unstable (half-life < 2 h) intergenic, cis-antisense, and intronic lncRNAs, as well as lncRNAs showing extreme stability (half-life > 16 h). Analysis of lncRNA features revealed that intergenic and cis-antisense RNAs are more stable than those derived from introns, as are spliced lncRNAs compared to unspliced (single exon) transcripts. Subcellular localization of lncRNAs indicated widespread trafficking to different cellular locations, with nuclear-localized lncRNAs more likely to be unstable. Surprisingly, one of the least stable lncRNAs is the well-characterized paraspeckle RNA Neat1, suggesting Neat1 instability contributes to the dynamic nature of this subnuclear domain. We have created an online interactive resource (http://stability. matticklab.com) that allows easy navigation of lncRNA and mRNA stability profiles and provides a comprehensive annotation of ∼7200 mouse lncRNAs.
Keyword Embryonic stem-cells
Messenger-RNA
Gene-expression
Nuclear-bodies
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
Institute for Molecular Bioscience - Publications
 
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