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Nucleic Acids Res. 2016 Aug 19;44(14):6949-60. doi: 10.1093/nar/gkw418. Epub 2016 May 12.

YB-1 regulates tiRNA-induced Stress Granule formation but not translational repression.

Author information

1
Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, MA 02115, USA Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
2
Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, MA 02115, USA.
3
Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, MA 02115, USA Department of Medicine, Harvard Medical School, Boston, MA 02115, USA panderson@rics.bwh.harvard.edu.
4
Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, MA 02115, USA Department of Medicine, Harvard Medical School, Boston, MA 02115, USA The Broad Institute of Harvard and M.I.T., Cambridge, MA 02142, USA pivanov@rics.bwh.harvard.edu.

Abstract

Stress-induced angiogenin (ANG)-mediated tRNA cleavage promotes a cascade of cellular events that starts with production of tRNA-derived stress-induced RNAs (tiRNAs) and culminates with enhanced cell survival. This stress response program relies on a subset tiRNAs that inhibit translation initiation and induce the assembly of stress granules (SGs), cytoplasmic ribonucleoprotein complexes with cytoprotective and pro-survival properties. SG-promoting tiRNAs bear oligoguanine motifs at their 5'-ends, assemble G-quadruplex-like structures and interact with the translational silencer YB-1. We used CRISPR/Cas9-based genetic manipulations and biochemical approaches to examine the role of YB-1 in tiRNA-mediated translational repression and SG assembly. We found that YB-1 directly binds to tiRNAs via its cold shock domain. This interaction is required for packaging of tiRNA-repressed mRNAs into SGs but is dispensable for tiRNA-mediated translational repression. Our studies reveal the functional role of YB-1 in the ANG-mediated stress response program.

PMID:
27174937
PMCID:
PMC5001593
DOI:
10.1093/nar/gkw418
[Indexed for MEDLINE]
Free PMC Article

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