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RGS4 RNA secondary structure mediates Staufen2 RNP assembly in Neurons

Fernández‐moya, SM; Ehses, J; Bauer, KE; Schieweck, R; Chakrabarti, AM; Lee, FCY; Illig, C; ... Kiebler, MA; + view all (2021) RGS4 RNA secondary structure mediates Staufen2 RNP assembly in Neurons. International Journal of Molecular Sciences , 22 (23) , Article 13021. 10.3390/ijms222313021. Green open access

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Abstract

RNA‐binding proteins (RBPs) act as posttranscriptional regulators controlling the fate of target mRNAs. Unraveling how RNAs are recognized by RBPs and in turn are assembled into neuronal RNA granules is therefore key to understanding the underlying mechanism. While RNA sequence elements have been extensively characterized, the functional impact of RNA secondary structures is only recently being explored. Here, we show that Staufen2 binds complex, long‐ranged RNA hairpins in the 3′‐untranslated region (UTR) of its targets. These structures are involved in the assembly of Staufen2 into RNA granules. Furthermore, we provide direct evidence that a defined Rgs4 RNA duplex regulates Staufen2‐dependent RNA localization to distal dendrites. Importantly, disrupting the RNA hairpin impairs the observed effects. Finally, we show that these secondary structures differently affect protein expression in neurons. In conclusion, our data reveal the importance of RNA secondary structure in regulating RNA granule assembly, localization and even-tually translation. It is therefore tempting to speculate that secondary structures represent an important code for cells to control the intracellular fate of their mRNAs.

Type: Article
Title: RGS4 RNA secondary structure mediates Staufen2 RNP assembly in Neurons
Open access status: An open access version is available from UCL Discovery
DOI: 10.3390/ijms222313021
Publisher version: https://doi.org/10.3390/ijms222313021
Language: English
Additional information: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).
Keywords: Staufen2; neuronal RNA granule; RNP assembly; RNA-binding protein; RNA localization; in vivo RNA binding
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Department of Neuromuscular Diseases
URI: https://discovery.ucl.ac.uk/id/eprint/10140025
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