Musashi interaction with poly(A)-binding protein is required for activation of target mRNA translation
| Autor: | Alan J. Tackett, Melanie C. MacNicol, Gwen V. Childs, Nicola K. Gray, Chad E. Cragle, Stephanie D. Byrum, Samuel G. Mackintosh, Angus M. MacNicol, Linda L. Hardy, William A. Richardson |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Cellular differentiation Xenopus Repressor Nerve Tissue Proteins Xenopus Proteins Polyadenylation Poly(A)-Binding Protein I Poly(A)-Binding Proteins Biochemistry Xenopus laevis 03 medical and health sciences Oogenesis PABPC1 Poly(A)-binding protein Animals RNA Messenger Molecular Biology Messenger RNA 030102 biochemistry & molecular biology biology Cell Cycle RNA-Binding Proteins Cell Differentiation Cell Biology biology.organism_classification Cell biology 030104 developmental biology Ribonucleoproteins Protein Biosynthesis Oocytes biology.protein Translational Activation Ectopic expression Signal Transduction |
| Zdroj: | J Biol Chem Cragle, C E, MacNicol, M C, Byrum, S D, Hardy, L L, Mackintosh, S G, Richardson, W A, Gray, N K, Childs, G V, Tackett, A J & MacNicol, A M 2019, ' Musashi interaction with poly(A) binding protein is required for activation of target mRNA translation ', Journal of Biological Chemistry, vol. 294, no. 28, pp. 10969-10986 . https://doi.org/10.1074/jbc.RA119.007220 |
| ISSN: | 0021-9258 |
| Popis: | The Musashi family of mRNA translational regulators control 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 mass spectrometry 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. Since 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. |
| Databáze: | OpenAIRE |
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