Examination of gene expression in cerebellum of mouse strains B6J, B6J-nmf205-/-, B6J-Gcn2-/- and B6J-nmf205-/-;Gcn2-/-.

ABSTRACT: Ribosome stalling during translation has recently been shown to cause neurodegeneration, yet the signaling pathways triggered by stalled elongation complexes are unknown. To investigate these pathways we analyzed the brain of B6J-nmf205-/- mice in which neuronal elongation complexes are stalled at AGA codons due to deficiencies in a tRNA Arg(UCU) tRNA and GTPBP2, a mammalian ribosome rescue factor. Increased levels of phosphorylation of eIF2α (Ser51) were detected prior to neurodegeneration in these mice and transcriptome analysis demonstrated activation of ATF4, a key transcription factor in the integrated stress response (ISR) pathway. Genetic experiments showed that this pathway was activated by the eIF2alpha kinase, GCN2, in an apparent deacylated tRNA-independent fashion. Further

ORGANISM(S): Mus musculus

SUBMITTER: Jeffrey Chuang 

PROVIDER: E-GEOD-79929 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress