Abstract
Background Alternative splicing, a ubiquitous phenomenon in eukaryotes, provides a regulatory mechanism for the biological diversity of individual genes. Most studies have focused on the effects of alternative splicing for protein synthesis. However, the influence of alternative splicing on the RNA subcellular localization has rarely been studied.
Results By analyzing RNA-seq data from subcellular fractions across thirteen human cell lines, we observed that splicing is apparent to promote cytoplasmic localization. We also discovered that intron retention is preferred by transcripts localized in the nucleus. Short and structurally stable introns show a positive correlation with nuclear localization. Such introns are predicted to be preferentially bound by MBNL1, an RNA-binding protein that contains two nuclear localization signals.
Conclusions Our findings reveal that alternative splicing plays an important role in regulating RNA subcellular localization. This study provides valuable clues for understanding the biological mechanisms of alternative splicing.
Abbreviations
- RNA FISH
- RNA fluorescent in situ hybridization;
- RNA-seq
- RNA sequencing;
- RBP
- RNA-binding protein;
- NLS
- nuclear signal sequence;
- ΔTU
- change of transcript usage;
- GO
- Gene Ontology;
- NMD
- nonsense-mediated decay;
- ΔΨ
- change of splicing inclusion;
- RI
- retained intron;
- SINE
- Short interspersed nuclear element;
- LINE
- Long interspersed nuclear element;
- LTR
- Long terminal repeat;
- GCR
- genetic compensation response;
- EJC
- exon-exon junction complex;
- TPM
- transcripts per million;
- A3
- alternative 3′ splice-site;
- A5
- alternative 5′ splice-site;
- AF
- alternative first exon;
- AL
- alternative last exon;
- MX
- mutually exclusive exon;
- SE
- skipping exon;
- Ribo-seq
- ribosome profiling;
