Insights into the control of mammalian mRNA splicing, translation and decay

Le 04 décembre 2023 à 14h00 Séminaire

At the post-transcriptional level, gene expression is controlled at multiple levels including pre-mRNA splicing, translation and mRNA decay. In addition, quality control mechanisms monitor the accuracy of gene expression and use post-transcriptional mechanism to trigger appropriate cellular responses. While studying the effects of anisomycin, a ribotoxin that perturbs protein synthesis, we discovered that ribotoxic stress leads to the reorganization of nuclear speckles. This response is accompanied by relocalization of immediate early gene (IEG) transcription foci to nuclear speckles and pronounced splicing activation of the corresponding pre-mRNAs. Our results assign nuclear speckles a new function as sites dedicated to the preferential expression of stress-induced genes. Covering subsequent steps of gene expression, I will introduce Ribo-Seq as the first method by which the kinetics of ribosome loading onto nascent mRNA can be measured within cells, and present our work on how IEG mRNAs are targeted for rapid degradation via CPEB4 associated to the Ccr4-Not deadenylase complex.