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Intron retention as a component of regulated gene expression programs

Published version
Peer-reviewed

Type

Article

Change log

Authors

Jacob, AG 
Smith, CWJ 

Abstract

Intron retention has long been an exemplar of regulated splicing with case studies of individual events serving as models that provided key mechanistic insights into the process of splicing control. In organisms such as plants and budding yeast, intron retention is well understood as a major mechanism of gene expression regulation. In contrast, in mammalian systems, the extent and functional significance of intron retention have, until recently, remained greatly underappreciated. Technical challenges to the global detection and quantitation of transcripts with retained introns have often led to intron retention being overlooked or dismissed as “noise”. Now, however, with the wealth of information available from high-throughput deep sequencing, combined with focused computational and statistical analyses, we are able to distinguish clear intron retention patterns in various physiological and pathological contexts. Several recent studies have demonstrated intron retention as a central component of gene expression programs during normal development as well as in response to stress and disease. Furthermore, these studies revealed various ways in which intron retention regulates protein isoform production, RNA stability and translation efficiency, and rapid induction of expression via post-transcriptional splicing of retained introns. In this review, we highlight critical findings from these transcriptomic studies and discuss commonalties in the patterns prevalent in intron retention networks at the functional and regulatory levels.

Description

Keywords

Cassette Exon, Intron Retention, Spinal Muscular Atrophy, Splice Factor, Splice Site, Animals, Gene Expression Regulation, Humans, Introns, Models, Genetic, Protein Biosynthesis, Protein Isoforms, RNA Stability

Journal Title

Human Genetics

Conference Name

Journal ISSN

0340-6717
1432-1203

Volume Title

Publisher

Springer
Sponsorship
Biotechnology and Biological Sciences Research Council (BB/J001457/1)
Wellcome Trust (092900/Z/10/Z)
British Heart Foundation (PG/16/28/32123)
Work in the authors’ lab has been funded by Grants from the British Heart Foundation (PG/16/28/32123), the Wellcome Trust (092900) and the BBSRC (BB/J001457/1).