title: Chromatin environment, transcriptional regulation, and splicing distinguish lincRNAs and mRNAs.
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.
authors.affiliation: Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts 02138, USA.|Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts 02142, USA.
authors.forename: Marta
authors.initials: M
authors.lastname: Melé
authors.affiliation: Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts 02138, USA.|Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts 02142, USA.|Department of Biological and Biomedical Sciences, Harvard University, Boston, Massachusetts 02115, USA.
authors.forename: Kaia
authors.initials: K
authors.lastname: Mattioli
authors.affiliation: Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts 02138, USA.|Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts 02142, USA.
authors.forename: William
authors.initials: W
authors.lastname: Mallard
authors.affiliation: Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts 02138, USA.|Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts 02142, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Shechner
authors.affiliation: Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts 02138, USA.|Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts 02142, USA.
authors.forename: Chiara
authors.initials: C
authors.lastname: Gerhardinger
authors.affiliation: Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts 02138, USA.|Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts 02142, USA.|Department of Pathology, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA.
authors.forename: John L
authors.initials: JL
authors.lastname: Rinn
mesh_terms: D001665:Binding Sites; D002843:Chromatin / Q000235:genetics*; D017124:Conserved Sequence / Q000235:genetics; D019143:Evolution, Molecular; D005091:Exons / Q000235:genetics; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D059372:Nucleotide Motifs / Q000235:genetics; D009928:Organ Specificity / Q000235:genetics; D011401:Promoter Regions, Genetic; D012326:RNA Splicing / Q000235:genetics; D020871:RNA Stability / Q000235:genetics; D062085:RNA, Long Noncoding / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D000072668:Splicing Factor U2AF / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D002843:Chromatin; D062085:RNA, Long Noncoding; D012333:RNA, Messenger; D000072668:Splicing Factor U2AF; D014157:Transcription Factors; C000607494:U2AF2 protein, human