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<p>The Musashi family of sequence-specific RNA binding proteins (Musashi1 and Musashi2) serve a critical role in mediating both physiological and pathological stem cell function in many tissue types by repressing the translation of target mRNAs that encode proteins that promote cell cycle inhibition and cell differentiation. In addition to repression of target mRNAs, we have also identified a role for Musashi proteins in activating the translation of target mRNAs in a context-dependent manner. However, the molecular mechanisms by which Musashi controls target mRNA translational activation have not been fully elucidated. Since Musashi lacks inherent enzymatic activity, its ability to modulate target mRNA translation likely involves recruitment of ancillary proteins to the target mRNA. We have previously identified a number of proteins that specifically associate with Musashi during <i>Xenopus laevis</i> oocyte maturation at a time when Musashi target mRNAs are translationally activated. Here, we demonstrate that one of these proteins, the Scd6/Like-sm family member LSM14B, is a mediator of the Musashi1-dependent mRNA translational activation that is required for oocyte maturation. Unlike previously characterized proteins which interact with the C-terminal domain of Musashi, LSM14B instead associates with the N-terminal RNA recognition motifs. Additionally, we demonstrate that the mammalian <i>Prop1</i> mRNA, which encodes a key regulator of pituitary development, is translationally activated by Musashi1 in a LSM14B-dependent manner. Our studies support an evolutionarily conserved role for LSM14B in facilitating the ability of Musashi1 to promote target mRNA translation.</p>

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Musashi-dependent mRNA translational activation is mediated through association with the Scd6/Like-sm family member, LSM14B

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年4月10日

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  • Katherine Bronson,
  • Jewel Banik,
  • Juchan Lim,
  • Milla M. Reddick,
  • Linda Hardy,
  • Gwen V. Childs,
  • Melanie C. MacNicol,
  • Angus M. MacNicol

摘要

The Musashi family of sequence-specific RNA binding proteins (Musashi1 and Musashi2) serve a critical role in mediating both physiological and pathological stem cell function in many tissue types by repressing the translation of target mRNAs that encode proteins that promote cell cycle inhibition and cell differentiation. In addition to repression of target mRNAs, we have also identified a role for Musashi proteins in activating the translation of target mRNAs in a context-dependent manner. However, the molecular mechanisms by which Musashi controls target mRNA translational activation have not been fully elucidated. Since Musashi lacks inherent enzymatic activity, its ability to modulate target mRNA translation likely involves recruitment of ancillary proteins to the target mRNA. We have previously identified a number of proteins that specifically associate with Musashi during Xenopus laevis oocyte maturation at a time when Musashi target mRNAs are translationally activated. Here, we demonstrate that one of these proteins, the Scd6/Like-sm family member LSM14B, is a mediator of the Musashi1-dependent mRNA translational activation that is required for oocyte maturation. Unlike previously characterized proteins which interact with the C-terminal domain of Musashi, LSM14B instead associates with the N-terminal RNA recognition motifs. Additionally, we demonstrate that the mammalian Prop1 mRNA, which encodes a key regulator of pituitary development, is translationally activated by Musashi1 in a LSM14B-dependent manner. Our studies support an evolutionarily conserved role for LSM14B in facilitating the ability of Musashi1 to promote target mRNA translation.