Lyons, ShawnAchorn, ChrisKedersha, NancyAnderson, PaulIvanov, Pavel2017-01-032016Lyons, Shawn M., Chris Achorn, Nancy L. Kedersha, Paul J. Anderson, and Pavel Ivanov. 2016. “YB-1 regulates tiRNA-induced Stress Granule formation but not translational repression.” Nucleic Acids Research 44 (14): 6949-6960. doi:10.1093/nar/gkw418. http://dx.doi.org/10.1093/nar/gkw418.0305-1048http://nrs.harvard.edu/urn-3:HUL.InstRepos:29738951Stress-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.en-USJournal Article2017-01-0310.1093/nar/gkw418