RESEARCH ARTICLE

Antisense transcription regulates the expression of sense gene via alternative polyadenylation

  • Ting Shen 1 ,
  • Huan Li 1 ,
  • Yifan Song 1 ,
  • Jun Yao 1 ,
  • Miao Han 1 ,
  • Ming Yu 2 ,
  • Gang Wei , 3 ,
  • Ting Ni , 3
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  • 1. Ministry of Education (MOE) Key Laboratory of Contemporary Anthropology, Collaborative Innovation Center of Genetics and Development, School of Life Sciences and Shanghai Cancer Center, Fudan University, Shanghai 200438, China
  • 2. Collaborative Innovation Center of Genetics and Development, Sheng Yushou Center of Cell Biology and Immunology, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China
  • 3. State Key Laboratory of Genetic Engineering, Collaborative Innovation Center of Genetics and Development, School of Life Sciences and Huashan Hospital, Fudan University, Shanghai 200438, China

Received date: 07 Sep 2017

Accepted date: 27 Nov 2017

Published date: 11 Jun 2018

Copyright

2017 The Author(s) 2017. This article is an open access publication

Abstract

Natural antisense transcripts (NAT) and alternative polyadenylation (APA) of messenger RNA (mRNA) are important contributors of transcriptome complexity, each playing a critical role in multiple biological processes. However, whether they have crosstalk and function collaboratively is unclear. We discovered that APA enriched in human sense-antisense (S-AS) gene pairs, and finally focused on RNASEH2C-KAT5 S-AS pair for further study. In cis but not in trans over-expression of the antisense KAT5 gene promoted the usage of distal polyA (pA) site in sense gene RNASEH2C, which generated longer 3′ untranslated region (3′UTR) and produced less protein, accompanying with slowed cell growth. Mechanistically, elevated Pol II occupancy coupled with SRSF3 could explain the higher usage of distal pA site. Finally, NAT-mediated downregulation of sense gene’s protein level in RNASEH2C-KAT5 pair was specific for human rather than mouse, which lacks the distal pA site of RNASEH2C. We provided the first evidence to support that certain gene affected phenotype may not by the protein of its own, but by affecting the expression of its overlapped gene through APA, implying an unexpected view for understanding the link between genotype and phenotype.

Cite this article

Ting Shen , Huan Li , Yifan Song , Jun Yao , Miao Han , Ming Yu , Gang Wei , Ting Ni . Antisense transcription regulates the expression of sense gene via alternative polyadenylation[J]. Protein & Cell, 2018 , 9(6) : 540 -552 . DOI: 10.1007/s13238-017-0497-0

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