PKR activation and eIF2α phosphorylation mediate human globin mRNA splicing at spliceosome assembly.

ABSTRACT: Short elements in mammalian mRNA can control gene expression by activating the RNA-dependent protein kinase PKR that attenuates translation by phosphorylating cytoplasmic eukaryotic initiation factor 2α (eIF2α). We demonstrate a novel, positive role for PKR activation and eIF2α phosphorylation in human globin mRNA splicing. PKR localizes in splicing complexes and associates with splicing factor SC35. Splicing and early-stage spliceosome assembly on β-globin pre-mRNA depend strictly on activation of PKR by a codon-containing RNA fragment within exon 1 and on phosphorylation of nuclear eIF2α on Serine 51. Nonphosphorylatable mutant eIF2αS51A blocked β-globin mRNA splicing in cells and nuclear extract. Mutations of the β-globin RNA activator abrogated PKR activation and profoundly affected mR

SUBMITTER: Ilan L 

PROVIDER: S-EPMC5520854 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature