输入蛋白β1介导与无义介导的RNA衰变相关因子的核输入。

Importin β1 mediates nuclear import of the factors associated with nonsense-mediated RNA decay.

作者信息

Hu Jianran, Li Ping, Shi Baozhong, Tie Jun

机构信息

Department of Biological Science and Technology, Changzhi University, Changzhi, 046011, China.

出版信息

Biochem Biophys Res Commun. 2021 Jan 20;542:34-39. doi: 10.1016/j.bbrc.2021.01.034.

DOI:10.1016/j.bbrc.2021.01.034

PMID:33486189

Abstract

In eukaryotic cells, nonsense-mediated RNA decay (NMD) is an essential physiological mechanism coupled to translation, regulating the stability of abnormal RNA containing premature termination codon (PTC) and a significant fraction of normal transcriptomes. So far, the molecular regulation mechanism of NMD pathway is far from fully elucidated. Previously, we observed the interaction between importin β1 (Impβ1) and UPF1, a core factor of NMD. Here, we demonstrated that Impβ1 knockdown stabilized NMD reporters, and Impβ1 and UPF1 interacted and co-regulated an extensive number of target transcripts. Furthermore, Impβ1 affected the interaction between UPF1 and SMG5 or MAGOH, and the nuclear distributions of UPF1, SMG1, SMG5 and MAGOH. Besides, Ran knockdown extremely promoted the dissociation of UPF1 from SMG5 or MAGOH. Our findings provide molecular insight into the potential function of Impβ1in nonsense-mediated RNA decay.

摘要

在真核细胞中，无义介导的RNA衰变（NMD）是一种与翻译偶联的重要生理机制，可调节含有提前终止密码子（PTC）的异常RNA以及相当一部分正常转录组的稳定性。到目前为止，NMD途径的分子调控机制尚未完全阐明。此前，我们观察到输入蛋白β1（Impβ1）与NMD的核心因子UPF1之间存在相互作用。在此，我们证明敲低Impβ1可使NMD报告基因稳定，并且Impβ1与UPF1相互作用并共同调节大量靶转录本。此外，Impβ1影响UPF1与SMG5或MAGOH之间的相互作用，以及UPF1、SMG1、SMG5和MAGOH的核分布。此外，敲低Ran可极大地促进UPF1与SMG5或MAGOH的解离。我们的研究结果为Impβ1在无义介导的RNA衰变中的潜在功能提供了分子层面的见解。