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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.

Original publication

DOI

10.1038/s41467-017-00454-2

Type

Journal article

Journal

Nat Commun

Publication Date

13/09/2017

Volume

8

Keywords

3' Untranslated Regions, Animals, Ataxia Telangiectasia Mutated Proteins, B-Lymphocytes, DNA Damage, Etoposide, Gene Expression Regulation, HEK293 Cells, Humans, Lymphocyte Activation, Mice, Inbred C57BL, Protein Biosynthesis, RNA, Messenger, T-Cell Intracellular Antigen-1, Tumor Suppressor Protein p53