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J Biol Chem. 2014 Mar 18. [Epub ahead of print]

Musashi-directed translational activation of target mRNAs is mediated by the poly[A] polymerase, Germline Development-2.

Author information

  • 1University of Arkansas for Medical Sciences, United States.

Abstract

The mRNA binding protein, Musashi, has been shown to regulate translation of select mRNAs and control cellular identity in both stem cells and cancer cells. Within mammalian cells, Musashi has traditionally been characterized as a repressor of translation. However, we have demonstrated that Musashi is an activator of translation in progesterone-stimulated oocytes of the frog Xenopus laevis, and recent evidence has revealed the capability of Musashi to function as an activator of translation in mammalian systems. The molecular mechanism by which Musashi directs activation of target mRNAs has not been elucidated. Here, we report a specific association of Musashi with the noncanonical poly[A] polymerase Germline Development-2 (GLD2) and map the association domain to 30 amino acids within the C-terminal domain of Musashi. We show that loss of GLD2 interaction through deletion of the binding domain, or treatment with antisense oligonucleotides compromises Musashi function. Additionally, we demonstrate that overexpression of both Musashi and GLD2 significantly enhances Musashi function. Finally, we report a similar co-association also occurs between murine Musashi and GLD2 orthologs, suggesting that coupling of Musashi to the polyadenylation apparatus is a conserved mechanism to promote target mRNA translation.

KEYWORDS:

Oocyte; Polyadenylation; RNA binding protein; Translation control; Xenopus

PMID:
24644291
[PubMed - as supplied by publisher]
PMCID:
PMC4022889
[Available on 2015/5/16]
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