Antisense transcription regulates the expression of sense gene via alternative polyadenylation.
10.1007/s13238-017-0497-0
- Author:
Ting SHEN
1
;
Huan LI
1
;
Yifan SONG
1
;
Jun YAO
1
;
Miao HAN
1
;
Ming YU
2
;
Gang WEI
3
;
Ting NI
4
Author Information
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. gwei@fudan.edu.cn.
4. 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. tingni@fudan.edu.cn.
- Publication Type:Journal Article
- Keywords:
3′UTR;
KAT5;
RNASEH2C;
alternative polyadenyaltion;
natural antisense transcripts
- MeSH:
Cell Proliferation;
genetics;
Evolution, Molecular;
Gene Expression Regulation;
genetics;
HEK293 Cells;
Humans;
Polyadenylation;
genetics;
RNA, Antisense;
genetics;
RNA, Messenger;
genetics;
Ribonuclease H;
genetics;
Serine-Arginine Splicing Factors;
metabolism;
Transcription, Genetic;
Up-Regulation;
genetics
- From:
Protein & Cell
2018;9(6):540-552
- CountryChina
- Language:English
-
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.
