Nat1 promotes translation of specific proteins that induce differentiation of mouse embryonic stem cells [expression]
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ABSTRACT: Nat1 (also known as p97/Dap5/Eif4g2) is a ubiquitously expressed cytoplasmic protein that is homologous to the C-terminal two thirds of eukaryotic translation initiation factor 4G (also known as Eif4g1). We previously showed that Nat1-null mouse embryonic stem cells (mESCs) were resistant to differentiation. In the current study, we found that Nat1 and Eif4g1 share many binding proteins, such as Eif3s, Eif4s and ribosomal proteins. However, Nat1 did not bind to Eif4e or poly A binding proteins, which are critical for cap-dependent translation initiation. In contrast, Nat1 binds to Eif2s, Fmr and related proteins, and Prrc2 proteins more preferentially than does Eif4g1. We also found that Nat1-null mESCs possess a status partially similar to ground state, which is established in wild-type mES cells when treated with inhibitors of the ERK and GSK3 signaling pathways. In Nat1-null mESCs, the ERK pathway is suppressed even without inhibitors. Ribosomal profiling revealed that translation of Map3k3 and Sos1 is suppressed in the absence of Nat1. Forced expression of Map3k3 induced differentiation of Nat1-null mESCs. These data collectively showed that Nat1 is involved in translation of proteins that are required for cell differentiation.
ORGANISM(S): Mus musculus
PROVIDER: GSE89007 | GEO | 2017/01/06
SECONDARY ACCESSION(S): PRJNA349775
REPOSITORIES: GEO
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