The importance of appropriately regulated AS is underscored by human diseases such as myotonic dystrophy that arise, not from aberrant splicing per se, but from mis-regulation of developmental programs of AS, with clinical symptoms arising from expression of mRNA isoforms at inappropriate stages of development (Cooper et al. Alternative cassette exons tend to affect intrinsically disordered protein regions, sites of protein–protein interactions, and sites of post-translational modifications, and programs of AS have the capacity to re-wire protein–protein interaction networks (Buljan et al. Numerous examples of the consequences of ASEs upon the function of pairs of protein isoforms have been well documented (Nilsen and Graveley 2010). Many alternative splicing events (ASEs) are regulated to ensure production of appropriate protein isoforms in the correct cellular environments. 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.Īlternative splicing (AS) is a widespread process, affecting the vast majority of human genes (Barbosa-Morais et al. 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.
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. 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.
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”. In contrast, in mammalian systems, the extent and functional significance of intron retention have, until recently, remained greatly underappreciated. In organisms such as plants and budding yeast, intron retention is well understood as a major mechanism of gene expression regulation. 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.
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