Ability of cell to properly express its genes depends on optimal transcription and splicing. RNA polymerase II transcribes protein-coding genes and produces pre-mRNAs, which cotranscriptionally undergo intron excision by the spliceosome, a megadalton RNA-protein complex. Spliceosome activation is a major, but poorly characterized control step, leading to a catalytically active complex. Our unpublished data identified a new pathway that controls spliceosome activation and links the regulation of transcription to the regulation of splicing. Notably, the pathway links three important cancer-related and therapeutically attractive proteins. We propose to apply proteomics and chemical biology approaches coupled to state-of-the-art genomics to characterize how the pathway activates the spliceosome and orchestrates interplay between transcription and splicing.

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