Global analysis of regulatory divergence in the evolution of mouse alternative polyadenylation

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 d...

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Main Authors:	Xiao, Mei‐Sheng, Zhang, Bin, Li, Yi‐Sheng, Gao, Qingsong, Sun, Wei, Chen, Wei
Format:	Online
Language:	English
Published:	John Wiley and Sons Inc. 2016
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5199128/

id	pubmed-5199128
recordtype	oai_dc
spelling	pubmed-51991282016-12-30 Global analysis of regulatory divergence in the evolution of mouse alternative polyadenylation Xiao, Mei‐Sheng Zhang, Bin Li, Yi‐Sheng Gao, Qingsong Sun, Wei Chen, Wei Articles 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 C57BL/6J and SPRET/EiJ mouse strains as well as allele‐specific APA pattern in their F1 hybrids. Among the 24,721 polyadenylation sites (pAs) from 7,271 genes expressing multiple pAs, we identified 3,747 pAs 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 pAs revealed that the local RNA secondary structure and a poly(U) tract in the upstream region could negatively modulate the pAs usage. John Wiley and Sons Inc. 2016-12-08 /pmc/articles/PMC5199128/ /pubmed/27932516 http://dx.doi.org/10.15252/msb.20167375 Text en © 2016 The Authors. Published under the terms of the CC BY 4.0 license This is an open access article under the terms of the Creative Commons Attribution 4.0 (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Xiao, Mei‐Sheng Zhang, Bin Li, Yi‐Sheng Gao, Qingsong Sun, Wei Chen, Wei
spellingShingle	Xiao, Mei‐Sheng Zhang, Bin Li, Yi‐Sheng Gao, Qingsong Sun, Wei Chen, Wei Global analysis of regulatory divergence in the evolution of mouse alternative polyadenylation
author_facet	Xiao, Mei‐Sheng Zhang, Bin Li, Yi‐Sheng Gao, Qingsong Sun, Wei Chen, Wei
author_sort	Xiao, Mei‐Sheng
title	Global analysis of regulatory divergence in the evolution of mouse alternative polyadenylation
title_short	Global analysis of regulatory divergence in the evolution of mouse alternative polyadenylation
title_full	Global analysis of regulatory divergence in the evolution of mouse alternative polyadenylation
title_fullStr	Global analysis of regulatory divergence in the evolution of mouse alternative polyadenylation
title_full_unstemmed	Global analysis of regulatory divergence in the evolution of mouse alternative polyadenylation
title_sort	global analysis of regulatory divergence in the evolution of mouse alternative polyadenylation
description	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 C57BL/6J and SPRET/EiJ mouse strains as well as allele‐specific APA pattern in their F1 hybrids. Among the 24,721 polyadenylation sites (pAs) from 7,271 genes expressing multiple pAs, we identified 3,747 pAs 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 pAs revealed that the local RNA secondary structure and a poly(U) tract in the upstream region could negatively modulate the pAs usage.
publisher	John Wiley and Sons Inc.
publishDate	2016
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5199128/
_version_	1613844443717173248

Global analysis of regulatory divergence in the evolution of mouse alternative polyadenylation

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