Department of Biochemistry, Biocenter, University of Würzburg, 97074, Würzburg, Germany.
European Research Institute for the Biology of Ageing (ERIBA), University Medical Center Groningen, University of Groningen, 9713 AV, Groningen, The Netherlands.
Nat Commun. 2019 Jun 3;10(1):2421. doi: 10.1038/s41467-019-10432-5.
Translation efficiency can be affected by mRNA stability and secondary structures, including G-quadruplex structures (G4s). The highly conserved DEAH-box helicase DHX36/RHAU resolves G4s on DNA and RNA in vitro, however a systems-wide analysis of DHX36 targets and function is lacking. We map globally DHX36 binding to RNA in human cell lines and find it preferentially interacting with G-rich and G4-forming sequences on more than 4500 mRNAs. While DHX36 knockout (KO) results in a significant increase in target mRNA abundance, ribosome occupancy and protein output from these targets decrease, suggesting that they were rendered translationally incompetent. Considering that DHX36 targets, harboring G4s, preferentially localize in stress granules, and that DHX36 KO results in increased SG formation and protein kinase R (PKR/EIF2AK2) phosphorylation, we speculate that DHX36 is involved in resolution of rG4 induced cellular stress.
翻译效率可能受到 mRNA 稳定性和二级结构的影响，包括 G-四链体结构 (G4s)。高度保守的 DEAH-box 解旋酶 DHX36/RHAU 在体外可解决 DNA 和 RNA 上的 G4s，但对 DHX36 靶标和功能的系统分析尚缺乏。我们在人细胞系中对 DHX36 与 RNA 的结合进行了全局映射，发现它优先与超过 4500 个 mRNA 上富含 G 和形成 G4 的序列相互作用。虽然 DHX36 敲除 (KO) 导致靶 mRNA 丰度显著增加，但这些靶标上的核糖体占据和蛋白质输出减少，表明它们的翻译能力丧失。考虑到含有 G4 的 DHX36 靶标优先定位于应激颗粒中，并且 DHX36 KO 导致 SG 形成和蛋白激酶 R (PKR/EIF2AK2) 磷酸化增加，我们推测 DHX36 参与解决 rG4 诱导的细胞应激。
