RNA processing and gene regulation

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The flow of genetic information from DNA to RNA to protein involves complex mechanisms of regulation, most of which act downstream of the process of transcription, which produces RNA molecules from a DNA template. RNA splicing is a process that eliminates non-coding intervening sequences from precursor RNAs and that joins together coding sequences to form the mature mRNA that is exported from the nucleus for translation to produce proteins in the cell. Sometimes, a series of different mRNA molecules can be produced from the same precursor RNA, in a process termed alternative splicing. This allows a single gene to increase its coding capacity, leading to the synthesis of structurally and functionally distinct forms of a protein that influence different cellular processes. We study the regulation of alternative splicing and how its misregulation can lead to human disease. We are also focusing on a surveillance mechanism, termed Nonsense-mediated decay or NMD, that eliminates mRNAs with premature termination codons that would otherwise give rise to truncated proteins that are potentially harmful for the cell. This is important since the NMD response affects the severity of up to one third of all human genetic diseases. We expect to facilitate a greater understanding of how the production of cellular RNAs is controlled, and how its dysregulation contributes to human disease.