Cargando…

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

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 differe...

Descripción completa

Detalles Bibliográficos
Autores principales: Melé, Marta, Mattioli, Kaia, Mallard, William, Shechner, David M., Gerhardinger, Chiara, Rinn, John L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5204342/
https://www.ncbi.nlm.nih.gov/pubmed/27927715
http://dx.doi.org/10.1101/gr.214205.116
_version_ 1782489881767837696
author Melé, Marta
Mattioli, Kaia
Mallard, William
Shechner, David M.
Gerhardinger, Chiara
Rinn, John L.
author_facet Melé, Marta
Mattioli, Kaia
Mallard, William
Shechner, David M.
Gerhardinger, Chiara
Rinn, John L.
author_sort Melé, Marta
collection PubMed
description 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.
format Online
Article
Text
id pubmed-5204342
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher Cold Spring Harbor Laboratory Press
record_format MEDLINE/PubMed
spelling pubmed-52043422017-01-17 Chromatin environment, transcriptional regulation, and splicing distinguish lincRNAs and mRNAs Melé, Marta Mattioli, Kaia Mallard, William Shechner, David M. Gerhardinger, Chiara Rinn, John L. Genome Res Research 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. Cold Spring Harbor Laboratory Press 2017-01 /pmc/articles/PMC5204342/ /pubmed/27927715 http://dx.doi.org/10.1101/gr.214205.116 Text en © 2017 Melé et al. Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/4.0/ This article, published in Genome Research, is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Research
Melé, Marta
Mattioli, Kaia
Mallard, William
Shechner, David M.
Gerhardinger, Chiara
Rinn, John L.
Chromatin environment, transcriptional regulation, and splicing distinguish lincRNAs and mRNAs
title Chromatin environment, transcriptional regulation, and splicing distinguish lincRNAs and mRNAs
title_full Chromatin environment, transcriptional regulation, and splicing distinguish lincRNAs and mRNAs
title_fullStr Chromatin environment, transcriptional regulation, and splicing distinguish lincRNAs and mRNAs
title_full_unstemmed Chromatin environment, transcriptional regulation, and splicing distinguish lincRNAs and mRNAs
title_short Chromatin environment, transcriptional regulation, and splicing distinguish lincRNAs and mRNAs
title_sort chromatin environment, transcriptional regulation, and splicing distinguish lincrnas and mrnas
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5204342/
https://www.ncbi.nlm.nih.gov/pubmed/27927715
http://dx.doi.org/10.1101/gr.214205.116
work_keys_str_mv AT melemarta chromatinenvironmenttranscriptionalregulationandsplicingdistinguishlincrnasandmrnas
AT mattiolikaia chromatinenvironmenttranscriptionalregulationandsplicingdistinguishlincrnasandmrnas
AT mallardwilliam chromatinenvironmenttranscriptionalregulationandsplicingdistinguishlincrnasandmrnas
AT shechnerdavidm chromatinenvironmenttranscriptionalregulationandsplicingdistinguishlincrnasandmrnas
AT gerhardingerchiara chromatinenvironmenttranscriptionalregulationandsplicingdistinguishlincrnasandmrnas
AT rinnjohnl chromatinenvironmenttranscriptionalregulationandsplicingdistinguishlincrnasandmrnas