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

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

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Sequence
  • Arsenites / pharmacology
  • Base Sequence
  • CRISPR-Cas Systems / genetics
  • Cell Proliferation
  • Cell Survival
  • Cytoplasmic Granules / drug effects
  • Cytoplasmic Granules / metabolism*
  • Eukaryotic Initiation Factor-4F / metabolism
  • Gene Deletion
  • Gene Knockout Techniques
  • Genetic Heterogeneity
  • Humans
  • MCF-7 Cells
  • Models, Molecular
  • Protein Biosynthesis* / drug effects
  • RNA, Guide / metabolism
  • RNA, Transfer / genetics
  • RNA, Transfer / metabolism*
  • Sodium Compounds / pharmacology
  • Stress, Physiological* / drug effects
  • Y-Box-Binding Protein 1 / chemistry
  • Y-Box-Binding Protein 1 / genetics
  • Y-Box-Binding Protein 1 / metabolism*

Substances

  • Arsenites
  • Eukaryotic Initiation Factor-4F
  • RNA, Guide
  • Sodium Compounds
  • Y-Box-Binding Protein 1
  • YBX1 protein, human
  • sodium arsenite
  • RNA, Transfer