A Slow Dynamic RNA Switch Regulates Processing of microRNA-21.

Autor: Shortridge MD; Department of Chemistry, University of Washington, Seattle, WA 98195-1700, USA., Olsen GL; Department of Chemistry, University of Washington, Seattle, WA 98195-1700, USA., Yang W; Department of Chemistry, University of Washington, Seattle, WA 98195-1700, USA; Greater Bay Biomedical Innocenter, Shenzhen Bay Laboratory, Shenzhen, Guangdong Province 518036, China., Walker MJ; Department of Chemistry, University of Washington, Seattle, WA 98195-1700, USA; Neoleukin Therapeutics, 188 East Blaine St, Suite 450, Seattle, WA 98102, USA., Varani G; Department of Chemistry, University of Washington, Seattle, WA 98195-1700, USA. Electronic address: varani@chem.washington.edu.
Jazyk: angličtina
Zdroj: Journal of molecular biology [J Mol Biol] 2022 Aug 30; Vol. 434 (16), pp. 167694. Date of Electronic Publication: 2022 Jun 23.
DOI: 10.1016/j.jmb.2022.167694
Abstrakt: The microRNAs are non-coding RNAs which post-transcriptionally regulate the expression of many eukaryotic genes, and whose dysregulation is a driver of human disease. Here we report the discovery of a very slow (0.1 s -1 ) conformational rearrangement at the Dicer cleavage site of pre-miR-21, which regulates the relative concentration of readily- and inefficiently-processed RNA structural states. We show that this dynamic switch is affected by single nucleotide mutations and can be biased by small molecule and peptide ligands, which can direct the microRNA to occupy the inefficiently processed state and reduce processing efficiency. This result reveals a new mechanism of RNA regulation and suggests a chemical approach to suppressing or activating pathogenic microRNAs by selective stabilization of their unprocessed or processed states.
Competing Interests: Declaration of Competing Interest The authors declare that they have competing financial interests; MDS and GV are co-founders of Ithax Pharmaceuticals and Ranar Therapeutics.
(Published by Elsevier Ltd.)
Databáze: MEDLINE
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