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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G4 解离酶 RHAU 调节 mRNA 翻译和稳定性以维持产后心脏功能和再生
DOI：
10.1074/jbc.ra120.014948
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发表时间：
2021-01
期刊：
影响因子：
--
通讯作者：
Yang Z
中科院分区：
文献类型：
--
作者：
Jiang M;Hu H;Zhao K;Di R;Huang X;Shi Y;Yue Y;Nie J;Yu S;Wang W;Yang Z
mRNA翻译和稳定性的转录后调节主要通过RNA结合蛋白实现，其对心脏功能越来越重要。此外，G-四链体（G4）和G4解离酶活性参与多种生物过程。然而，G4解离酶活性在心脏功能中的作用仍然未知。本研究的目的是探讨RNA解旋酶与腺苷酸和尿苷酸丰富的元素（RHAU），RNA结合蛋白与G4解离酶活性在出生后的心脏功能，通过删除RHAU在出生后的小鼠心肌细胞中的作用。RHAU缺陷小鼠表现出进行性病理性重塑，导致心力衰竭和死亡率，并损害新生儿心脏再生。RHAU消融降低了Yap 1和Hexim 1的蛋白水平，但增强了其mRNA水平，这两种蛋白是心脏发育和出生后心脏功能的重要调节因子。此外，发现RHAU与这些基因的5'和3' UTR两者相关联以使mRNA不稳定并增强翻译。因此，我们已经证明了RHAU在mRNA翻译和稳定性的双重调节中的重要功能，这对心脏生理学至关重要。
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.