The TIA1 RNA-Binding Protein Family Regulates EIF2AK2-Mediated Stress Response and Cell Cycle Progression

• Published in: Molecular cell Vol. 69; no. 4; pp. 622 - 635.e6
• Main Authors: Meyer, Cindy, Garzia, Aitor, Mazzola, Michael, Gerstberger, Stefanie, Molina, Henrik, Tuschl, Thomas
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.02.2018
• Subjects: alternative splicing; Animalia; apoptosis; binding sites; Cell Cycle; complementary DNA; CRISPR-Cas Systems; Cytoplasmic Granules - metabolism; double-stranded RNA; eIF-2 Kinase - genetics; eIF-2 Kinase - metabolism; eukaryotic translation initiation factor 2 alpha kinase 2; HEK293 Cells; Humans; integrated stress response; interferon-inducible double-stranded RNA-dependent protein kinase activator A; introns; messenger RNA; phenotype; protein kinases; Regulatory Sequences, Ribonucleic Acid; RNA Splice Sites; RNA Splicing; RNA, Double-Stranded - genetics; RNA, Double-Stranded - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism; RNA-binding proteins; RNA-Binding Proteins - antagonists & inhibitors; RNA-Binding Proteins - genetics; RNA-Binding Proteins - metabolism; stress response; Stress, Physiological; T-Cell Intracellular Antigen-1 - antagonists & inhibitors; T-Cell Intracellular Antigen-1 - genetics; T-Cell Intracellular Antigen-1 - metabolism; T-cell restricted intracellular antigen-1; translation (genetics); Uridine - metabolism; interferon-inducible double-stranded RNA-dependent protein kinase activator A; alternative splicing; eukaryotic translation initiation factor 2 alpha kinase 2; cell cycle; apoptosis; T-cell restricted intracellular antigen-1; integrated stress response

TIA1 and TIAL1 encode a family of U-rich element mRNA-binding proteins ubiquitously expressed and conserved in metazoans. Using PAR-CLIP, we determined that both proteins bind target sites with identical specificity in 3′ UTRs and introns proximal to 5′ as well as 3′ splice sites. Double knockout (D...