The G4 resolvase RHAU modulates mRNA translation and stability to sustain postnatal heart function and regeneration
The G4 resolvase RHAU modulates mRNA translation and stability to sustain postnatal heart function and regeneration
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DOI：
10.1074/jbc.ra120.014948
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Zhongzhou Yang
中科院分区：
文献类型：
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作者：
Mingyang Jiang;Han Hu;Ke Zhao;Ruomin Di;Xinyi Huang;Yingchao Shi;Yunyun Yue;Junwei Nie;Shan Yu;Wengong Wang;Zhongzhou Yang
Post-transcriptional regulation of mRNA translation and stability is primarily achieved by RNA-binding proteins, which are of increasing importance for heart function. Furthermore, G-quadruplex (G4) and G4 resolvase activity are involved in a variety of biological processes. However, the role of G4 resolvase activity in heart function remains unknown. The present study aims to investigate the role of RNA helicase associated with adenylate- and uridylate-rich element (RHAU), an RNA-binding protein with G4 resolvase activity in postnatal heart function through deletion of Rhau in the cardiomyocytes of postnatal mice. RHAU-deficient mice displayed progressive pathological remodeling leading to heart failure and mortality and impaired neonatal heart regeneration. RHAU ablation reduced the protein levels but enhanced mRNA levels of Yap1 and Hexim1 that are important regulators for heart development and postnatal heart function. Furthermore, RHAU was found to associate with both the 5' and 3' UTRs of these genes to destabilize mRNA and enhance translation. Thus, we have demonstrated the important functions of RHAU in the dual regulation of mRNA translation and stability, which is vital for heart physiology.
