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., and Rasko, John E.J. (2017) Intron retention enhances gene regulatory complexity in vertebrates. Genome Biology, 18. 216.

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DOI: 10.1186%2Fs13059-017-1339-3
View at Publisher Website: https://doi.org/10.1186%2Fs13059-017-133...
 
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Abstract

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.

Item ID: 68983
Item Type: Article (Research - C1)
ISSN: 1474-760X
Keywords: Transcriptomic complexity, Granulocytes, Evolution, Alternative splicing, Intron retention, Gene regulation
Copyright Information: © The Author(s). 2017 Open Access This 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.
Funders: National Health and Medical Research Council (NHMRC)
Projects and Grants: NHMRC grant number: #1061906, NHMRC grant number: #1080530, NHMRC grant number: #1044754, NHMRC grant number: #1086020, NHMRC grant number: #1126306
Date Deposited: 28 Sep 2021 23:27
FoR Codes: 31 BIOLOGICAL SCIENCES > 3104 Evolutionary biology > 310403 Biological adaptation @ 10%
31 BIOLOGICAL SCIENCES > 3102 Bioinformatics and computational biology > 310204 Genomics and transcriptomics @ 60%
31 BIOLOGICAL SCIENCES > 3105 Genetics > 310508 Genome structure and regulation @ 30%
SEO Codes: 28 EXPANDING KNOWLEDGE > 2801 Expanding knowledge > 280102 Expanding knowledge in the biological sciences @ 100%
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