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Musashi interaction with poly(A)-binding protein is required for activation of target mRNA translation.

Authors :
Cragle CE
MacNicol MC
Byrum SD
Hardy LL
Mackintosh SG
Richardson WA
Gray NK
Childs GV
Tackett AJ
MacNicol AM
Source :
The Journal of biological chemistry [J Biol Chem] 2019 Jul 12; Vol. 294 (28), pp. 10969-10986. Date of Electronic Publication: 2019 May 31.
Publication Year :
2019

Abstract

The Musashi family of mRNA translational regulators controls both physiological and pathological stem cell self-renewal primarily by repressing target mRNAs that promote differentiation. In response to differentiation cues, Musashi can switch from a repressor to an activator of target mRNA translation. However, the molecular events that distinguish Musashi-mediated translational activation from repression are not understood. We have previously reported that Musashi function is required for the maturation of Xenopus oocytes and specifically for translational activation of specific dormant maternal mRNAs. Here, we employed MS to identify cellular factors necessary for Musashi-dependent mRNA translational activation. We report that Musashi1 needs to associate with the embryonic poly(A)-binding protein (ePABP) or the canonical somatic cell poly(A)-binding protein PABPC1 for activation of Musashi target mRNA translation. Co-immunoprecipitation studies demonstrated an increased Musashi1 interaction with ePABP during oocyte maturation. Attenuation of endogenous ePABP activity severely compromised Musashi function, preventing downstream signaling and blocking oocyte maturation. Ectopic expression of either ePABP or PABPC1 restored Musashi-dependent mRNA translational activation and maturation of ePABP-attenuated oocytes. Consistent with these Xenopus findings, PABPC1 remained associated with Musashi under conditions of Musashi target mRNA de-repression and translation during mammalian stem cell differentiation. Because association of Musashi1 with poly(A)-binding proteins has previously been implicated only in repression of Musashi target mRNAs, our findings reveal novel context-dependent roles for the interaction of Musashi with poly(A)-binding protein family members in response to extracellular cues that control cell fate.<br /> (© 2019 Cragle et al.)

Details

Language :
English
ISSN :
1083-351X
Volume :
294
Issue :
28
Database :
MEDLINE
Journal :
The Journal of biological chemistry
Publication Type :
Academic Journal
Accession number :
31152063
Full Text :
https://doi.org/10.1074/jbc.RA119.007220