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Intron retention enhances gene regulatory complexity in vertebrates.

Intron retention enhances gene regulatory complexity in vertebrates.
Author Information (click to view)

Schmitz U, Pinello N, Jia F, Alasmari S, Ritchie W, Keightley MC, Shini S, Lieschke GJ, Wong JJ, Rasko JEJ,


Schmitz U, Pinello N, Jia F, Alasmari S, Ritchie W, Keightley MC, Shini S, Lieschke GJ, Wong JJ, Rasko JEJ, (click to view)

Schmitz U, Pinello N, Jia F, Alasmari S, Ritchie W, Keightley MC, Shini S, Lieschke GJ, Wong JJ, Rasko JEJ,

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Genome biology 2017 11 1618(1) 216 doi 10.1186/s13059-017-1339-3
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.

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