ADAR1 deaminase contributes to scheduled skeletal myogenesis progression via stage-specific functions.
Adenosine deaminases acting on RNA 1 (ADAR1) catalyzes cellular RNA adenosine-to-inosine editing events on structured RNA molecules. In line with this critical role, ADAR1 exhibits ubiquitous expression and is essential for embryonic development. However, regulation and developmental significance of this RNA editor in a spatiotemporal context are largely elusive. Here we unveil a novel tissue-specific role of ADAR1 in skeletal myogenesis. ADAR1 expression displayed programmed alteration that is coordinated with differentiation cues, and mediated negatively by miRNA-1/206. Coincidently, ADAR1 exerts stage-dependent functions-suppression of apoptosis at the onset of differentiation and preservation of timely myotube formation through later phase. Furthermore, the post-transcriptional aspect of its myogenic role was illustrated by the spectrum of binding RNAs, as revealed by high-throughput approach, as well as by direct regulation of myogenesis-associated targets such as dynamin 1/2 (Dnm1/2) and annexin A4. Consequently, maintenance of target gene expression profiles likely contributes to a state of cytoskeleton and membrane dynamics that is amenable to myoblast morphogenesis. Collectively, these findings uncover a critical link of ADAR1 to myogenesis, and further highlight an epigenetic mechanism by which ADAR1 and miR-1/206 interplay to control scheduled myoblast-myotube transition.
Department of Biomedical Sciences, Graduate Institute of Biomedical Sciences, College of Medicine, Tao-Yuan, Taiwan.
C-L
CL
Hsieh
Molecular Medicine Research Center, Chang Gung University, Tao-Yuan, Taiwan.
H
H
Liu
Molecular Medicine Research Center, Chang Gung University, Tao-Yuan, Taiwan.
Y
Y
Huang
BGI-Shenzhen, Shenzhen, China.
L
L
Kang
Department of Biomedical Sciences, Graduate Institute of Biomedical Sciences, College of Medicine, Tao-Yuan, Taiwan.
H-W
HW
Chen
1] Department of Biomedical Sciences, Graduate Institute of Biomedical Sciences, College of Medicine, Tao-Yuan, Taiwan [2] Molecular Medicine Research Center, Chang Gung University, Tao-Yuan, Taiwan.
Y-T
YT
Chen
Department of Biomedical Sciences, Graduate Institute of Biomedical Sciences, College of Medicine, Tao-Yuan, Taiwan.
Y-R
YR
Wee
1] Department of Biomedical Sciences, Graduate Institute of Biomedical Sciences, College of Medicine, Tao-Yuan, Taiwan [2] Molecular Medicine Research Center, Chang Gung University, Tao-Yuan, Taiwan.
S-J
SJ
Chen
1] Department of Biomedical Sciences, Graduate Institute of Biomedical Sciences, College of Medicine, Tao-Yuan, Taiwan [2] Molecular Medicine Research Center, Chang Gung University, Tao-Yuan, Taiwan.
B C-M
BC
Tan
D000243:Adenosine Deaminase / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D048708:Cell Growth Processes / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000166:cytology / Q000201:enzymology* / Q000254:growth & development*; D016601:RNA-Binding Proteins / Q000378:metabolism*
D016601:RNA-Binding Proteins; C567955:ADARB1 protein, human; D000243:Adenosine Deaminase