Open AccessPan‐tissue analysis of allelic alternative polyadenylation suggests widespread functional regulation
Author(s) -
Li Yisheng,
Schaefke Bernhard,
Zou Xudong,
Zhang Min,
Heyd Florian,
Sun Wei,
Zhang Bin,
Li Guipeng,
Liang Weizheng,
He Yuhao,
Zhou Juexiao,
Li Yunfei,
Fang Liang,
Hu Yuhui,
Chen Wei
Publication year - 2020
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.20199367
Subject(s) - biology , polyadenylation , allele , genetics , computational biology , evolutionary biology , gene , gene expression
Alternative polyadenylation ( APA ) is a major layer of gene regulation. However, it has recently been argued that most APA represents molecular noise. To clarify their functional relevance and evolution, we quantified allele‐specific APA patterns in multiple tissues from an F1 hybrid mouse. We found a clearly negative correlation between gene expression and APA diversity for the 2,866 genes (24.9%) with a dominant polyadenylation site ( PAS ) usage above or equal to 90%, suggesting that their other PAS s represent molecular errors. Among the remaining genes with multiple PAS s, 3,971 genes (34.5%) express two or more isoforms with potentially functional importance. Interestingly, the genes with potentially functional minor PAS s specific to neuronal tissues often express two APA isoforms with distinct subcellular localizations. Furthermore, our analysis of cis ‐ APA divergence shows its pattern across tissues is distinct from that of gene expression. Finally, we demonstrate that the relative usage of alternative PAS s is not only affected by their cis ‐regulatory elements, but also by potential coupling between transcriptional and APA regulation as well as competition kinetics between alternative sites.