Antisense transcription regulates the expression of sense gene via alternative polyadenylation

doi:10.1007/s13238-017-0497-0

Protein Cell

2018, Vol. 9

Issue (6) : 540-552 https://doi.org/10.1007/s13238-017-0497-0

RESEARCH ARTICLE

Antisense transcription regulates the expression of sense gene via alternative polyadenylation

Ting Shen¹, Huan Li¹, Yifan Song¹, Jun Yao¹, Miao Han¹, Ming Yu², Gang Wei³(

), Ting Ni³(

)

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

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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.

Keywords natural antisense transcripts alternative polyadenyaltion 3′UTR RNASEH2C KAT5

Corresponding Author(s): Gang Wei,Ting Ni

Issue Date: 11 June 2018

Cite this article:

Ting Shen,Huan Li,Yifan Song, et al. Antisense transcription regulates the expression of sense gene via alternative polyadenylation[J]. Protein Cell, 2018, 9(6): 540-552.

URL:

https://academic.hep.com.cn/pac/EN/10.1007/s13238-017-0497-0
https://academic.hep.com.cn/pac/EN/Y2018/V9/I6/540

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