Post-transcriptional Regulation of Nkx2-5 by RHAU in Heart Development

作者：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 · 发表于：Cell Reports · 年份：2015 · DOI：10.1016/j.celrep.2015.09.043 · 被引用次数：89 · 研究领域：RNA and protein synthesis mechanisms、RNA Research and Splicing、RNA modifications and cancer

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.