Selectively Constrained RNA Editing Regulation Crosstalks with piRNA Biogenesis in Primates.
Although millions of RNA editing events have been reported to modify hereditary information across the primate transcriptome, evidence for their functional significance remains largely elusive, particularly for the vast majority of editing sites in noncoding regions. Here, we report a new mechanism for the functionality of RNA editing-a crosstalk with PIWI-interacting RNA (piRNA) biogenesis. Exploiting rhesus macaque as an emerging model organism closely related to human, in combination with extensive genome and transcriptome sequencing in seven tissues of the same animal, we deciphered accurate RNA editome across both long transcripts and the piRNA species. Superimposing and comparing these two distinct RNA editome profiles revealed 4,170 editing-bearing piRNA variants, or epiRNAs, that primarily derived from edited long transcripts. These epiRNAs represent distinct entities that evidence an intersection between RNA editing regulations and piRNA biogenesis. Population genetics analyses in a macaque population of 31 independent animals further demonstrated that the epiRNA-associated RNA editing is maintained by purifying selection, lending support to the functional significance of this crosstalk in rhesus macaque. Correspondingly, these findings are consistent in human, supporting the conservation of this mechanism during the primate evolution. Overall, our study reports the earliest lines of evidence for a crosstalk between selectively constrained RNA editing regulation and piRNA biogenesis, and further illustrates that such an interaction may contribute substantially to the diversification of the piRNA repertoire in primates.
Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, Peking University, Beijing, China.
Xin-Zhuang
XZ
Yang
Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, Peking University, Beijing, China.
Jia-Yu
JY
Chen
Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, Peking University, Beijing, China.
Chu-Jun
CJ
Liu
Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, Peking University, Beijing, China.
Jiguang
J
Peng
Department of Biomedical Sciences and Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan Molecular Medicine Research Center, Chang Gung University, Tao-Yuan, Taiwan.
Yin Rei
YR
Wee
Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, Peking University, Beijing, China.
Xiaorui
X
Han
Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, Peking University, Beijing, China Peking-Tsinghua Center for Life Sciences, Beijing, China Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China.
Chenqu
C
Wang
Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, Peking University, Beijing, China.
Xiaoming
X
Zhong
Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, Peking University, Beijing, China.
Qing Sunny
QS
Shen
Department of Biomedical Sciences and Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan Molecular Medicine Research Center, Chang Gung University, Tao-Yuan, Taiwan.
Hsuan
H
Liu
Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, Peking University, Beijing, China.
Huiqing
H
Cao
Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, Peking University, Beijing, China Peking-Tsinghua Center for Life Sciences, Beijing, China Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China.
Xiao-Wei
XW
Chen
Department of Biomedical Sciences and Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan Molecular Medicine Research Center, Chang Gung University, Tao-Yuan, Taiwan chuanyunli@pku.edu.cn btan@mail.cgu.edu.tw.
Bertrand Chin-Ming
BC
Tan
Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, Peking University, Beijing, China chuanyunli@pku.edu.cn btan@mail.cgu.edu.tw.
Chuan-Yun
CY
Li
D000818:Animals; D006801:Humans; D008253:Macaca mulatta / Q000235:genetics* / Q000378:metabolism; D023421:Models, Animal; D017393:RNA Editing; D034741:RNA, Small Interfering / Q000096:biosynthesis* / Q000235:genetics; D017423:Sequence Analysis, RNA / Q000379:methods*; D059467:Transcriptome
D034741:RNA, Small Interfering
RNA editing; RNA-Seq; piRNA biogenesis; population genetics; rhesus macaque; whole-genome sequencing