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First intron length in mammals is associated with 5’ exon skipping rate

Seung Gu Park, Sridhar Hannenhalli
doi: https://doi.org/10.1101/024463
Seung Gu Park
Center for Bioinformatics and Computational Biology University of Maryland, College Park, MD, USA
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  • For correspondence: seung2u@umiacs.umd.edu sridhar@umiacs.umd.edu
Sridhar Hannenhalli
Center for Bioinformatics and Computational Biology University of Maryland, College Park, MD, USA
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  • For correspondence: seung2u@umiacs.umd.edu sridhar@umiacs.umd.edu
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Abstract

The first introns in eukaryotes are much longer than downstream introns. While the functional roles of large first introns have been studied extensively, investigations into the mechanisms leading up to extreme lengths are limited. Prominently, Hong et al. noted that the first introns are predominantly in 5’ UTR and suggested that its lengthening may have resulted from a 5’-ward shifting of donor site due to a lower selection on splice site, as well as a selection to occlude upstream cryptic translation start sites. Here we suggest exon skipping as an alternative mechanism for first intron lengthening. Exon skipping results in consecutive introns becoming part of a single longer intron. We reasoned that a 5’-biased exon skipping rate could lead to longer introns toward the 5’-end of the gene, especially the first intron. Based on multiple datasets in human and mouse, we indeed found that internal exons toward the 5’-end of the gene are skipped significantly more frequently than the downstream exons. Importantly, we show that 5’-biased exon skipping is supported by consistent 5’-bias in several genomic, epigenomic, contextual, and evolutionary features that can be functionally linked to exon skipping. Interestingly, we found that first introns are enriched for relics of, now defunct, exons, some of which may have been recruited for regulatory functions; a significantly greater-than-expected fraction of such exons are included in cDNAs in other mammals. Overall, our results offer 5’-biased exon skipping as a novel, and arguably more potent, alternative explanation for substantially lengthening of first introns.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted August 12, 2015.
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First intron length in mammals is associated with 5’ exon skipping rate
Seung Gu Park, Sridhar Hannenhalli
bioRxiv 024463; doi: https://doi.org/10.1101/024463
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First intron length in mammals is associated with 5’ exon skipping rate
Seung Gu Park, Sridhar Hannenhalli
bioRxiv 024463; doi: https://doi.org/10.1101/024463

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