title: YB-1 regulates tiRNA-induced Stress Granule formation but not translational repression.
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.
authors.affiliation: 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.
authors.forename: Shawn M
authors.initials: SM
authors.lastname: Lyons
authors.affiliation: Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, MA 02115, USA.
authors.forename: Chris
authors.initials: C
authors.lastname: Achorn
authors.affiliation: 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.
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Kedersha
authors.affiliation: 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.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Anderson
authors.affiliation: 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.
authors.forename: Pavel
authors.initials: P
authors.lastname: Ivanov
mesh_terms: D000595:Amino Acid Sequence; D018053:Arsenites / Q000494:pharmacology; D001483:Base Sequence; D064113:CRISPR-Cas Systems / Q000235:genetics; D049109:Cell Proliferation; D002470:Cell Survival; D003594:Cytoplasmic Granules / Q000187:drug effects / Q000378:metabolism*; D039562:Eukaryotic Initiation Factor-4F / Q000378:metabolism; D017353:Gene Deletion; D055786:Gene Knockout Techniques; D018740:Genetic Heterogeneity; D006801:Humans; D061986:MCF-7 Cells; D008958:Models, Molecular; D014176:Protein Biosynthesis / Q000187:drug effects; D000094704:RNA, Guide, CRISPR-Cas Systems / Q000378:metabolism; D012343:RNA, Transfer / Q000235:genetics / Q000378:metabolism*; D017670:Sodium Compounds / Q000494:pharmacology; D013312:Stress, Physiological / Q000187:drug effects; D051840:Y-Box-Binding Protein 1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D018053:Arsenites; D039562:Eukaryotic Initiation Factor-4F; D000094704:RNA, Guide, CRISPR-Cas Systems; D017670:Sodium Compounds; D051840:Y-Box-Binding Protein 1; C070856:YBX1 protein, human; C017947:sodium arsenite; D012343:RNA, Transfer