Control of RNA processing during RNA polymerase II transcription

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Cells must convert information encoded in DNA into protein-coding messenger (m)RNA or regulatory non-coding (nc)RNAs, which is achieved through a process of RNA polymerase II (Pol II) transcription. During Pol II transcription eukaryotic RNA precursors are processed into their mature functional form. Defects in regulation of RNA processing are associated with neurodegenerative disorders and cancer. Although importance of Pol II transcription in regulation of RNA processing is well established, the underlying molecular mechanisms are poorly understood. Building upon our recent discoveries, we propose that transcription factors associated with the transcribing Pol II, mediate RNA processing by regulating activity of the RNA processing enzymes during transcription. This proposal aims to uncover underlying regulatory mechanisms, factors involved and their functional contribution to gene expression to test our hypothesis. The mechanistic insight generated by this work will uncover universal principles that govern gene regulation, inform on how dysregulated transcription could lead to human disease and in the long term guide development of future therapeutic approaches with improved specificity of targeting.