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Alternative splicing at GYNNGY 5' splice sites: more noise, less regulation.

Abstract：

:Numerous eukaryotic genes are alternatively spliced. Recently, deep transcriptome sequencing has skyrocketed proportion of alternatively spliced genes; over 95% human multi-exon genes are alternatively spliced. One fundamental question is: are all these alternative splicing (AS) events functional? To look into this issue, we studied the most common form of alternative 5' splice sites-GYNNGYs (Y = C/T), where both GYs can function as splice sites. Global analyses suggest that splicing noise (due to stochasticity of splicing process) can cause AS at GYNNGYs, evidenced by higher AS frequency in non-coding than in coding regions, in non-conserved than in conserved genes and in lowly expressed than in highly expressed genes. However, ∼20% AS GYNNGYs in humans and ∼3% in mice exhibit tissue-dependent regulation. Consistent with being functional, regulated GYNNGYs are more conserved than unregulated ones. And regulated GYNNGYs have distinctive sequence features which may confer regulation. Particularly, each regulated GYNNGY comprises two splice sites more resembling each other than unregulated GYNNGYs, and has more conserved downstream flanking intron. Intriguingly, most regulated GYNNGYs may tune gene expression through coupling with nonsense-mediated mRNA decay, rather than encode different proteins. In summary, AS at GYNNGY 5' splice sites is primarily splicing noise, and secondarily a way of regulation.

journal_name

Nucleic Acids Res

journal_title

Nucleic acids research

authors

Wang M,Zhang P,Shu Y,Yuan F,Zhang Y,Zhou Y,Jiang M,Zhu Y,Hu L,Kong X,Zhang Z

doi

10.1093/nar/gku1253

subject

Has Abstract

pub_date

2014-12-16 00:00:00

pages

13969-80

issue

22

eissn

0305-1048

issn

1362-4962

pii

gku1253

journal_volume

42

pub_type

杂志文章

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