Mex-3B induces apoptosis by inhibiting miR-92a access to the Bim-3'UTR

Oncogene
Takeaki OdaTetsu Akiyama

Abstract

Cells respond to a variety of cellular stresses, including DNA damage, by regulating genes whose expression modulates cell cycle arrest, DNA repair, senescence, and/or apoptosis. MicroRNAs (miRNAs) play essential roles in both normal development and disease pathogenesis by destabilizing mRNAs and inhibiting translation. In turn, miRNA biogenesis, turnover, and activity can be regulated by specific RNA-binding proteins. Here we show that Mex-3B, an hnRNP K homology (KH) domain-containing RNA-binding protein, critically modulates DNA stress-induced apoptosis by posttranscriptionally upregulating the pro-apoptotic BH3 (Bcl-2 homology region 3)-only family member Bim. Furthermore, our data indicate that binding of Mex-3B to the 3'-untranslated region (3'UTR) of Bim interferes with the interaction of an Argonaute (Ago)-miR-92a complex with a miR-92a target site present in the Bim RNA. Our results provide novel insights into the posttranscriptional mechanisms that are critical for cellular stress responses.

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Citations

Jul 29, 2020·International Journal of Molecular Sciences·Simon Jasinski-BergnerBarbara Seliger

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Methods Mentioned

BETA
transfection
immunoprecipitation
FACS
pull-down
PAR-CLIP
electrophoretic mobility shift
PCR
Assay
flow cytometry
PCRs

Software Mentioned

MultiGauge
RNAfold
miRanda
TargetScan

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