Post-transcriptional Regulation of Nkx2-5 by RHAU in Heart Development
Post-transcriptional Regulation of Nkx2-5 by RHAU in Heart Development
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RHAU 在心脏发育中对 Nkx2-5 的转录后调控
DOI：
10.1016/j.celrep.2015.09.043
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发表时间：
2015-10-27
期刊：
影响因子：
8.8
通讯作者：
Yang, Zhongzhou
中科院分区：
文献类型：
--
作者：
Nie, Junwei;Jiang, Mingyang;Yang, Zhongzhou
RNAG-四联体(G4S)在RNA生物学中起着重要作用。然而，mRNA G-四联体在胚胎发育中的作用和调控仍不清楚。以前，我们确定RHAU(DHX36，G4R1)是一种RNA解旋酶，它能分解mRNA的G-四链体。在这里，我们发现Rhau基因的心脏缺失会导致小鼠心脏缺陷和胚胎死亡。基因表达谱证实Nkx2-5mRNA是RHAU的靶标，与其5‘和3’UTRs相关，并调节其稳定性和翻译。Nkx2-5mRNA的5‘非编码区含有一个G-四链体，需要RHAU进行蛋白质翻译，而Nkx2-5的3’非编码区含有一个富含AU的元件(ARE)，促进了RHAU介导的mRNA衰变。因此，我们揭示了心脏发育过程中Nkx2-5转录后调控的机制。同时，本研究还证实了5‘非编码区G-四链介导的蛋白质翻译在器官发生中的作用。
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.