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Tia1 dependent regulation of mRNA subcellular location and translation controls p53 expression in B cells

Author

Listed:
  • Manuel D. Díaz-Muñoz

    (The Babraham Institute
    Centre de Physiopathologie Toulouse-Purpan, INSERM UMR1043 / CNRS U5282)

  • Vladimir Yu. Kiselev

    (The Babraham Institute
    Wellcome Trust Genome Campus)

  • Nicolas Le Novère

    (The Babraham Institute)

  • Tomaz Curk

    (University of Ljubljana, Faculty of Computer and Information Science)

  • Jernej Ule

    (UCL Institute of Neurology
    The Crick Institute)

  • Martin Turner

    (The Babraham Institute)

Abstract

Post-transcriptional regulation of cellular mRNA is essential for protein synthesis. Here we describe the importance of mRNA translational repression and mRNA subcellular location for protein expression during B lymphocyte activation and the DNA damage response. Cytoplasmic RNA granules are formed upon cell activation with mitogens, including stress granules that contain the RNA binding protein Tia1. Tia1 binds to a subset of transcripts involved in cell stress, including p53 mRNA, and controls translational silencing and RNA granule localization. DNA damage promotes mRNA relocation and translation in part due to dissociation of Tia1 from its mRNA targets. Upon DNA damage, p53 mRNA is released from stress granules and associates with polyribosomes to increase protein synthesis in a CAP-independent manner. Global analysis of cellular mRNA abundance and translation indicates that this is an extended ATM-dependent mechanism to increase protein expression of key modulators of the DNA damage response.

Suggested Citation

  • Manuel D. Díaz-Muñoz & Vladimir Yu. Kiselev & Nicolas Le Novère & Tomaz Curk & Jernej Ule & Martin Turner, 2017. "Tia1 dependent regulation of mRNA subcellular location and translation controls p53 expression in B cells," Nature Communications, Nature, vol. 8(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-00454-2
    DOI: 10.1038/s41467-017-00454-2
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