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Nat Commun. 2017 Sep 13;8(1):530. doi: 10.1038/s41467-017-00454-2.

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

Author information

1
Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Cambridge, CB22 3AT, UK. manuel.diaz-munoz@babraham.ac.uk.
2
Centre de Physiopathologie Toulouse-Purpan, INSERM UMR1043 / CNRS U5282, Toulouse, 31300, France. manuel.diaz-munoz@babraham.ac.uk.
3
Laboratory of Signalling, The Babraham Institute, Cambridge, CB22 3AT, UK.
4
Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, CB10 1SA, UK.
5
University of Ljubljana, Faculty of Computer and Information Science, Ljubljana, Slovenia.
6
Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, WC1N 3BG, UK.
7
The Crick Institute, 1 Midland Road, London, NW1 1AT, UK.
8
Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Cambridge, CB22 3AT, UK.

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.Sequestering mRNA in cytoplasmic stress granules is a mechanism for translational repression. Here the authors find that p53 mRNA, present in stress granules in activated B lymphocytes, is released upon DNA damage and is translated in a CAP-independent manner.

PMID:
28904350
PMCID:
PMC5597594
DOI:
10.1038/s41467-017-00454-2
[Indexed for MEDLINE]
Free PMC Article

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