Format

Send to

Choose Destination
Nucleic Acids Res. 2014 Dec 16;42(22):13969-80. doi: 10.1093/nar/gku1253. Epub 2014 Nov 26.

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

Author information

1
State Key Laboratory of Medical Genomics, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China Graduate School of the Chinese Academy of Sciences, Beijing, People's Republic of China.
2
State Key Laboratory of Medical Genomics, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China Graduate School of the Chinese Academy of Sciences, Beijing, People's Republic of China xykong@sibs.ac.cn.
3
Institute of Molecular Evolutionary Genetics and Department of Biology, Pennsylvania State University, University Park, PA 16802, USA zhangz.sci@gmail.com.

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.

PMID:
25428370
PMCID:
PMC4267661
DOI:
10.1093/nar/gku1253
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Silverchair Information Systems Icon for PubMed Central
Loading ...
Support Center