Post-transcriptional Regulation of Nkx2-5 by RHAU in Heart Development.
RNA G-quadruplexes (G4s) play important roles in RNA biology. However, the function and regulation of mRNA G-quadruplexes in embryonic development remain elusive. Previously, we identified RHAU (DHX36, G4R1) as an RNA helicase that resolves mRNA G-quadruplexes. Here, we find that cardiac deletion of Rhau leads to heart defects and embryonic lethality in mice. Gene expression profiling identified Nkx2-5 mRNA as a target of RHAU that associates with its 5' and 3' UTRs and modulates its stability and translation. The 5' UTR of Nkx2-5 mRNA contains a G-quadruplex that requires RHAU for protein translation, while the 3' UTR of Nkx2-5 mRNA possesses an AU-rich element (ARE) that facilitates RHAU-mediated mRNA decay. Thus, we uncovered the mechanisms underlying Nkx2-5 post-transcriptional regulation during heart development. Meanwhile, this study demonstrates the function of mRNA 5' UTR G-quadruplex-mediated protein translation in organogenesis.
State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University, Nanjing 210061, China.
Junwei
J
Nie
State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University, Nanjing 210061, China.
Mingyang
M
Jiang
The MOE Key Laboratory for Cell Proliferation and Regulation Biology, Institute of Cell Biology, College of Life Sciences, Beijing Normal University, Beijing 100875, China.
Xiaotian
X
Zhang
Department of Biochemistry and Molecular Biology, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
Hao
H
Tang
State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University, Nanjing 210061, China.
Hengwei
H
Jin
State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University, Nanjing 210061, China.
Xinyi
X
Huang
State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University, Nanjing 210061, China.
Baiyin
B
Yuan
State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University, Nanjing 210061, China.
Chenxi
C
Zhang
Friedrich Miescher Institute for Biomedical Research, Basel 4058, Switzerland.
Janice Ching
JC
Lai
Friedrich Miescher Institute for Biomedical Research, Basel 4058, Switzerland.
Yoshikuni
Y
Nagamine
State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University, Nanjing 210061, China.
Dejing
D
Pan
Department of Biochemistry and Molecular Biology, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China. Electronic address: wwg@bjmu.edu.cn.
Wengong
W
Wang
State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University, Nanjing 210061, China. Electronic address: zhongzhouyang@nju.edu.cn.
Zhongzhou
Z
Yang
D020413:3' Untranslated Regions / Q000235:genetics; D020121:5' Untranslated Regions / Q000235:genetics; D000818:Animals; D015152:Blotting, Northern; D019556:COS Cells; D002460:Cell Line; D002522:Chlorocebus aethiops; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism*; D054856:G-Quadruplexes; D006321:Heart / Q000196:embryology; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D051379:Mice; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics*
D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins; C095552:NKX2-5 protein, human; D014157:Transcription Factors; D053487:DEAD-box RNA Helicases