Open AccessGlobal analysis of regulatory divergence in the evolution of mouse alternative polyadenylation
Author(s) -
Xiao MeiSheng,
Zhang Bin,
Li YiSheng,
Gao Qingsong,
Sun Wei,
Chen Wei
Publication year - 2016
Publication title -
molecular systems biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 8.523
H-Index - 148
ISSN - 1744-4292
DOI - 10.15252/msb.20167375
Subject(s) - polyadenylation , biology , genetics , gene , alternative splicing , rna splicing , allele , functional divergence , regulatory sequence , trans acting , regulation of gene expression , gene expression , computational biology , exon , rna , gene family , mutant
Alternative polyadenylation ( APA ), which is regulated by both cis ‐elements and trans ‐factors, plays an important role in post‐transcriptional regulation of eukaryotic gene expression. However, comparing to the extensively studied transcription and alternative splicing, the extent of APA divergence during evolution and the relative cis‐ and trans ‐contribution remain largely unexplored. To directly address these questions for the first time in mammals, by using deep sequencing‐based methods, we measured APA divergence between C57 BL /6J and SPRET /EiJ mouse strains as well as allele‐specific APA pattern in their F1 hybrids. Among the 24,721 polyadenylation sites ( pA s) from 7,271 genes expressing multiple pA s, we identified 3,747 pA s showing significant divergence between the two strains. After integrating the allele‐specific data from F1 hybrids, we demonstrated that these events could be predominately attributed to cis ‐regulatory effects. Further systematic sequence analysis of the regions in proximity to cis ‐divergent pA s revealed that the local RNA secondary structure and a poly(U) tract in the upstream region could negatively modulate the pA s usage.