Small-molecule Ro-08-2750 interacts with many RNA-binding proteins and elicits MUSASHI2-independent phenotypes.
RNA-binding protein
small-molecule inhibitor
steroid hormones
Journal
RNA (New York, N.Y.)
ISSN: 1469-9001
Titre abrégé: RNA
Pays: United States
ID NLM: 9509184
Informations de publication
Date de publication:
10 2023
10 2023
Historique:
received:
20
01
2023
accepted:
13
06
2023
medline:
20
9
2023
pubmed:
28
6
2023
entrez:
27
6
2023
Statut:
ppublish
Résumé
RNA-binding proteins (RBPs) are key regulators of gene expression. Small molecules targeting these RBP-RNA interactions are a rapidly emerging class of therapeutics for treating a variety of diseases. Ro-08-2750 (Ro) is a small molecule identified as a competitive inhibitor of Musashi (MSI)-RNA interactions. Here, we show that multiple Ro-dependent cellular phenotypes, specifically adrenocortical steroid production and cell viability, are Musashi-2 (MSI2)-independent. Using an unbiased proteome-wide approach, we discovered Ro broadly interacts with RBPs, many containing RRM domains. To confirm this finding, we leveraged the large-scale ENCODE data to identify a subset of RBPs whose depletion phenocopies Ro inhibition, indicating Ro is a promiscuous inhibitor of multiple RBPs. Consistent with broad disruption of ribonucleoprotein complexes, Ro treatment leads to stress granule formation. This strategy represents a generalizable framework for validating the specificity and identifying targets of RBP inhibitors in a cellular context.
Identifiants
pubmed: 37369529
pii: rna.079605.123
doi: 10.1261/rna.079605.123
pmc: PMC10578479
doi:
Substances chimiques
RNA-Binding Proteins
0
RNA
63231-63-0
Proteome
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
1458-1470Subventions
Organisme : NIGMS NIH HHS
ID : R35 GM147025
Pays : United States
Informations de copyright
© 2023 Walters et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.
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