Post-transcriptional Regulation of Nkx2-5 by RHAU in Heart Development
Junwei Nie,
Mingyang Jiang,
Xiaotian Zhang,
Hao Tang,
Hengwei Jin,
Xinyi Huang,
Baiyin Yuan,
Chenxi Zhang,
Janice Ching Lai,
Yoshikuni Nagamine,
Dejing Pan,
Wengong Wang,
Zhongzhou Yang
Affiliations
Junwei 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 Jiang
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
Xiaotian Zhang
The MOE Key Laboratory for Cell Proliferation and Regulation Biology, Institute of Cell Biology, College of Life Sciences, Beijing Normal University, Beijing 100875, China
Hao Tang
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
Hengwei 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 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 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 Zhang
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
Janice Ching Lai
Friedrich Miescher Institute for Biomedical Research, Basel 4058, Switzerland
Yoshikuni Nagamine
Friedrich Miescher Institute for Biomedical Research, Basel 4058, Switzerland
Dejing Pan
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
Wengong Wang
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
Zhongzhou Yang
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
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.
