RT Journal Article
T1 Synergistic regulation of Rgs4 mRNA by HuR and miR-26/RISC in neurons
A1 Ehses, Janina
A1 Fernández-Moya, Sandra M.
A1 Schröger, Luise
A1 Kiebler, Michael A.
K1 Proteínas
AB 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 destabilizing Rgs4 mRNA. Interestingly, in smooth muscle cells, Rgs4 is stabilized by HuR, indicating tissue-dependent differences in HuR function. Using in vitro RNA-based pulldown experiments, we identify the functional AU-rich element (ARE) within the Rgs4 3ʹ-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 reporterassays. 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.
PB Taylor and Francis online
YR 2020
FD 2020-08-11
LK https://hdl.handle.net/10630/45503
UL https://hdl.handle.net/10630/45503
LA eng
NO Ehses, J., Fernández-Moya, S. M., Schröger, L., & Kiebler, M. A. (2021). Synergistic regulation of Rgs4 mRNA by HuR and miR-26/RISC in neurons. RNA Biology, 18(7), 988–998. https://doi.org/10.1080/15476286.2020.1795409
NO Deutsche Forschungsgemeinschaft
NO Friedrich-Baur-Stiftung
NO Austrian Science Fund
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 3 mar 2026