The eukaryotic translation initiation factor eIF4E reprogrammes alternative splicing

ABSTRACT: Aberrant splicing is typically attributed to splice-factor (SF) mutation and contributes to malignancies including acute myeloid leukemia (AML). Here, we discovered a mutation-independent means to extensively reprogramme alternative splicing (AS). We showed that dysregulated expression of eukaryotic translation initiation factor eIF4E elevated selective splice factor production, thereby impacting multiple spliceosome complexes, including factors mutated in AML such as SF3B1 and U2AF1. These changes generated a splicing landscape that predominantly supported altered splice-site selection for ~800 transcripts in cell lines and ~4600 transcripts in specimens from high-eIF4E AML patients otherwise harbouring no known SF mutations. Nuclear RNA immunoprecipitations, export assays, polysome analy

SUBMITTER: Dr. Mehdi Ghram 

PROVIDER: S-SCDT-10_15252-EMBJ_2021110496 | biostudies-other |

REPOSITORIES: biostudies-other