Dr Steve West
Dr West’s laboratory studies the mechanisms of RNA synthesis and processing in human cells. These pathways are absolutely essential for all cellular functions and their associated defects are among the most common underlying causes of disease. Without exception, all transcribed needs to be processed to acquire full function. Our main interest is the synthesis of RNAs that code for proteins, which are synthesised by RNA polymerase II (Pol II) as pre-mRNA transcripts. These are matured into mRNA by capping, splicing and cleavage and polyadenylation.
mRNA maturation needs to be extremely accurate to preserve reading frame but it also needs to retain plasticity to allow for the alternative processing that generates full proteome diversity. Although tremendously complex, these reactions occur remarkably quickly. This is achieved through their coordination with transcription such that most mRNA maturation is in fact co-transcriptional.
Dr West and his research group use cutting edge genetic experiments with downstream transcriptomic and proteomic approaches address these mechanisms. Broadly speaking, there are two main research questions.
- What are the mechanisms that couple transcription and RNA processing?
- How is co-transcriptional RNA processing quality controlled to prevent aberrant RNA expression?
- Davidson L, Muniz L and West S. 3′ end formation of pre-mRNA and phosphorylation of Ser2 on the RNA polymerase II CTD are reciprocally coupled in human cells. Genes and Development. 2014 Feb 15; 28(4):342-56
- Davidson L, Kerr A and West S. Co-transcriptional degradation of aberrant pre-mRNA by Xrn2. EMBO Journal. 2012 Apr 20; 31(11):2566-78
- West S, Proudfoot NJ and Dye MJ. Molecular dissection of mammalian RNA polymerase II transcriptional termination. Molecular Cell. 2008; March 14; 29(5):600-610
- West S, Gromak N, Norbury CJ and Proudfoot NJ. Adenylation and exosome-mediated degradation of cotranscriptionally cleaved pre-messenger RNA in human cells. Molecular Cell. February 3; 21(3): 437-443
- West S*, Gromak N* and Proudfoot NJ., Human 5′ –> 3′ exonuclease Xrn2 promotes transcription termination at co-transcriptional cleavage sites. 2004. November 25; 432 (7016): 522-525