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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...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory Press
2017
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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 |
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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 |
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