Synergistic regulation ofRgs4mRNA by HuR and miR-26/RISC in neurons

Ehses, Janina; Fernandez-Moya, Sandra M.; Schroeger, Luise und Kiebler, Michael A. (2020): Synergistic regulation ofRgs4mRNA by HuR and miR-26/RISC in neurons. In: Rna Biology, Bd. 18, Nr. 7: S. 988-998

Abstract

The negative regulator of G-protein signalling 4 (Rgs4) is linked to several neurologic diseases,e.g. schizophrenia, addiction, seizure and pain perception. Consequently, Rgs4 expression is tightly regulated, resulting in high mRNA and protein turnover. The post-transcriptional control of gene expression is mediated via RNA-binding proteins (RBPs) that interact with mRNAs in a combinatorial fashion. Here, we show that in neurons the RBP HuR reduces endogenous Rgs4 expression by destabilizingRgs4mRNA. Interestingly, in smooth muscle cells,Rgs4is stabilized by HuR, indicating tissue-dependent differences in HuR function. Usingin vitroRNA-based pulldown experiments, we identify the functional AU-rich element (ARE) within theRgs43MODIFIER LETTER PRIME-UTR that is recognized and bound by HuR. Bioinformatic analysis uncovered that this ARE lies within a highly conserved area next to a miR-26 binding site. We find that the neuronal-enriched miR-26 negatively influences Rgs4 expression in neurons. Further, HuR and miR-26 act synergistically in fluorescent reporter assays. Together, our data suggest a regulatory mechanism, in which an RBP selectively destabilizes a target mRNA in cooperation with a miRNA and the RISC machinery.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 1547-6286
• Sprache: Englisch