First Author | Nie J | Year | 2015 |
Journal | Cell Rep | Volume | 13 |
Issue | 4 | Pages | 723-732 |
PubMed ID | 26489465 | Mgi Jnum | J:265627 |
Mgi Id | MGI:6201954 | Doi | 10.1016/j.celrep.2015.09.043 |
Citation | Nie J, et al. (2015) Post-transcriptional Regulation of Nkx2-5 by RHAU in Heart Development. Cell Rep 13(4):723-732 |
abstractText | 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. |