Nucleoporin 107 facilitates the nuclear export of Scn5a mRNA to regulate cardiac bioelectricity.

ABSTRACT: Nucleoporins (Nups) are known to be functional in nucleo-cytoplasmic transport, but the roles of nucleoporins in nonproliferating cells, such as cardiac myocytes, are still poorly understood. In this study, we report that Nup107 regulates cardiac bioelectricity by controlling the nucleo-cytoplasmic trafficking of Scn5a mRNA. Overexpression of Nup107 induced the protein expression of Scn5a rather than that of other ion channels, with no effects of their mRNA levels. The analysis for the protein production demonstrated Nup107-facilitated transport of Scn5a mRNA. Using RIP-PCR and luciferase assay, we found that the 5'-UTR of Scn5a mRNA was not involved in the interaction, whereas the spatial interaction between Nup107 protein and Scn5a mRNA was formed when Scn5a mRNA passing through the nuclear pore. Functionally, Nup107 overexpression in neonatal rat ventricle myocytes significantly increased the currents of Scn5a-encoded INa channel. Moreover, the close correlation between Nup107 and Nav1.5 protein expression was observed in cardiomycytes and heart tissues subjected to hypoxia and ischaemic insults, suggesting a fast regulation of Nup107 on Nav1.5 channel in cardiac myocytes in a posttranscriptional manner. These findings may provide insights into the emergent control of cardiac electrophysiology through Nup-mediated modulation of ion channels.

SUBMITTER: Guan Y 

PROVIDER: S-EPMC6349201 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature