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Chromatin environment, transcriptional regulation, and splicing distinguish lincRNAs and mRNAs

Marta Melé, Kaia Mattioli, William Mallard, David M Shechner, Chiara Gerhardinger, John Rinn
doi: https://doi.org/10.1101/088484
Marta Melé
1Department of Stem Cell and Regenerative Biology, Harvard University, 7 Divinity Avenue, Cambridge, Massachusetts 02138, USA
2Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts 02142, USA
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Kaia Mattioli
1Department of Stem Cell and Regenerative Biology, Harvard University, 7 Divinity Avenue, Cambridge, Massachusetts 02138, USA
2Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts 02142, USA
3Department of Biological and Biomedical Sciences, Harvard University, Boston, Massachusetts 02115, USA
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William Mallard
1Department of Stem Cell and Regenerative Biology, Harvard University, 7 Divinity Avenue, Cambridge, Massachusetts 02138, USA
2Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts 02142, USA
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David M Shechner
1Department of Stem Cell and Regenerative Biology, Harvard University, 7 Divinity Avenue, Cambridge, Massachusetts 02138, USA
2Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts 02142, USA
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Chiara Gerhardinger
1Department of Stem Cell and Regenerative Biology, Harvard University, 7 Divinity Avenue, Cambridge, Massachusetts 02138, USA
2Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts 02142, USA
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John Rinn
1Department of Stem Cell and Regenerative Biology, Harvard University, 7 Divinity Avenue, Cambridge, Massachusetts 02138, USA
2Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts 02142, USA
4Department of Pathology, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA
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ABSTRACT

While long intergenic noncoding RNAs (lincRNAs) and mRNAs share similar biogenesis pathways, these transcript classes differ in many regards. LincRNAs are less evolutionarily conserved, less abundant, and more tissue-specific, suggesting that their pre‐ and post-transcriptional regulation is different from that of mRNAs. Here, we perform an in-depth characterization of the features that contribute to lincRNA regulation in multiple human cell lines. We find that lincRNA promoters are depleted of transcription factor (TF) binding sites, yet enriched for some specific factors such as GATA and FOS relative to mRNA promoters. Surprisingly, we find that H3K9me3—a histone modification typically associated with transcriptional repression—is more enriched at the promoters of active lincRNA loci than at those of active mRNAs. Moreover, H3K9me3-marked lincRNA genes are more tissue-specific. The most discriminant differences between lincRNAs and mRNAs involve splicing. LincRNAs are less efficiently spliced, which cannot be explained by differences in U1 binding or the density of exonic splicing enhancers, but may be partially attributed to lower U2AF65 binding and weaker splicing–related motifs. Conversely, the stability of lincRNAs and mRNAs is similar, differing only with regard to the location of stabilizing protein binding sites. Finally, we find that certain transcriptional properties are correlated with higher evolutionary conservation in both DNA and RNA motifs, and are enriched in lincRNAs that have been functionally characterized.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
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Posted November 17, 2016.
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Chromatin environment, transcriptional regulation, and splicing distinguish lincRNAs and mRNAs
Marta Melé, Kaia Mattioli, William Mallard, David M Shechner, Chiara Gerhardinger, John Rinn
bioRxiv 088484; doi: https://doi.org/10.1101/088484
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Chromatin environment, transcriptional regulation, and splicing distinguish lincRNAs and mRNAs
Marta Melé, Kaia Mattioli, William Mallard, David M Shechner, Chiara Gerhardinger, John Rinn
bioRxiv 088484; doi: https://doi.org/10.1101/088484

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