Post-transcriptional regulation of Gene Expression

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The flow of genetic information from DNA to RNA to protein involves complex mechanisms of regulation acting downstream of the process of transcription, which produces RNA molecules from a DNA template. Pre-mRNA splicing is the process by which non-coding intervening sequences (introns) are excised from precursor RNAs and coding sequences (exons) are joined to form the mature messenger RNA. A further level of complexity is added by alternative splicing, where a series of different mRNA molecules can be produced by the differential use of splice sites within a pre-mRNA, enabling a single gene to increase its coding capacity. We will study the regulation of Alternative splicing, in particular related to its coupling to the process of transcription. We are investigating a cellular process that controls the quality of RNA produced by cells, termed Nonsense-mediated decay (NMD), which degrades RNAs that encode harmful proteins for the cell. We will focus on a specialised NMD machinery that is localised to the endoplasmic reticulum (ER) and has a role during cellular stress. Finally, we will study the mechanism by which short non-coding RNAs (termed microRNAs) are produced from longer intricately folded precursors and regulate the expression of cellular mRNAs. Our research programme is at the basic end of the spectrum. We expect to contribute to a greater understanding on how the production of cellular RNAs is tightly controlled and how its dysregulation can contribute to human disease. We rely on a variety of experimental systems, including mammalian cell lines in culture, nematodes (C. elegans) and mouse models and we use cell biological, biochemical and single-molecule approaches.