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Intron retention enhances gene regulatory complexity in vertebrates

BACKGROUND: While intron retention (IR) is now widely accepted as an important mechanism of mammalian gene expression control, it remains the least studied form of alternative splicing. To delineate conserved features of IR, we performed an exhaustive phylogenetic analysis in a highly purified and f...

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Autores principales: Schmitz, Ulf, Pinello, Natalia, Jia, Fangzhi, Alasmari, Sultan, Ritchie, William, Keightley, Maria-Cristina, Shini, Shaniko, Lieschke, Graham J., Wong, Justin J-L, Rasko, John E. J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5688624/
https://www.ncbi.nlm.nih.gov/pubmed/29141666
http://dx.doi.org/10.1186/s13059-017-1339-3
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author Schmitz, Ulf
Pinello, Natalia
Jia, Fangzhi
Alasmari, Sultan
Ritchie, William
Keightley, Maria-Cristina
Shini, Shaniko
Lieschke, Graham J.
Wong, Justin J-L
Rasko, John E. J.
author_facet Schmitz, Ulf
Pinello, Natalia
Jia, Fangzhi
Alasmari, Sultan
Ritchie, William
Keightley, Maria-Cristina
Shini, Shaniko
Lieschke, Graham J.
Wong, Justin J-L
Rasko, John E. J.
author_sort Schmitz, Ulf
collection PubMed
description BACKGROUND: While intron retention (IR) is now widely accepted as an important mechanism of mammalian gene expression control, it remains the least studied form of alternative splicing. To delineate conserved features of IR, we performed an exhaustive phylogenetic analysis in a highly purified and functionally defined cell type comprising neutrophilic granulocytes from five vertebrate species spanning 430 million years of evolution. RESULTS: Our RNA-sequencing-based analysis suggests that IR increases gene regulatory complexity, which is indicated by a strong anti-correlation between the number of genes affected by IR and the number of protein-coding genes in the genome of individual species. Our results confirm that IR affects many orthologous or functionally related genes in granulocytes. Further analysis uncovers new and unanticipated conserved characteristics of intron-retaining transcripts. We find that intron-retaining genes are transcriptionally co-regulated from bidirectional promoters. Intron-retaining genes have significantly longer 3′ UTR sequences, with a corresponding increase in microRNA binding sites, some of which include highly conserved sequence motifs. This suggests that intron-retaining genes are highly regulated post-transcriptionally. CONCLUSIONS: Our study provides unique insights concerning the role of IR as a robust and evolutionarily conserved mechanism of gene expression regulation. Our findings enhance our understanding of gene regulatory complexity by adding another contributor to evolutionary adaptation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13059-017-1339-3) contains supplementary material, which is available to authorized users.
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spelling pubmed-56886242017-11-22 Intron retention enhances gene regulatory complexity in vertebrates Schmitz, Ulf Pinello, Natalia Jia, Fangzhi Alasmari, Sultan Ritchie, William Keightley, Maria-Cristina Shini, Shaniko Lieschke, Graham J. Wong, Justin J-L Rasko, John E. J. Genome Biol Research BACKGROUND: While intron retention (IR) is now widely accepted as an important mechanism of mammalian gene expression control, it remains the least studied form of alternative splicing. To delineate conserved features of IR, we performed an exhaustive phylogenetic analysis in a highly purified and functionally defined cell type comprising neutrophilic granulocytes from five vertebrate species spanning 430 million years of evolution. RESULTS: Our RNA-sequencing-based analysis suggests that IR increases gene regulatory complexity, which is indicated by a strong anti-correlation between the number of genes affected by IR and the number of protein-coding genes in the genome of individual species. Our results confirm that IR affects many orthologous or functionally related genes in granulocytes. Further analysis uncovers new and unanticipated conserved characteristics of intron-retaining transcripts. We find that intron-retaining genes are transcriptionally co-regulated from bidirectional promoters. Intron-retaining genes have significantly longer 3′ UTR sequences, with a corresponding increase in microRNA binding sites, some of which include highly conserved sequence motifs. This suggests that intron-retaining genes are highly regulated post-transcriptionally. CONCLUSIONS: Our study provides unique insights concerning the role of IR as a robust and evolutionarily conserved mechanism of gene expression regulation. Our findings enhance our understanding of gene regulatory complexity by adding another contributor to evolutionary adaptation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13059-017-1339-3) contains supplementary material, which is available to authorized users. BioMed Central 2017-11-16 /pmc/articles/PMC5688624/ /pubmed/29141666 http://dx.doi.org/10.1186/s13059-017-1339-3 Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Schmitz, Ulf
Pinello, Natalia
Jia, Fangzhi
Alasmari, Sultan
Ritchie, William
Keightley, Maria-Cristina
Shini, Shaniko
Lieschke, Graham J.
Wong, Justin J-L
Rasko, John E. J.
Intron retention enhances gene regulatory complexity in vertebrates
title Intron retention enhances gene regulatory complexity in vertebrates
title_full Intron retention enhances gene regulatory complexity in vertebrates
title_fullStr Intron retention enhances gene regulatory complexity in vertebrates
title_full_unstemmed Intron retention enhances gene regulatory complexity in vertebrates
title_short Intron retention enhances gene regulatory complexity in vertebrates
title_sort intron retention enhances gene regulatory complexity in vertebrates
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5688624/
https://www.ncbi.nlm.nih.gov/pubmed/29141666
http://dx.doi.org/10.1186/s13059-017-1339-3
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