Dr Shona Murphy
The research carried out by my group is aimed at understanding fundamental mechanisms controlling expression of human genes and has focused, for several years, on the genes encoding the small nuclear (sn) RNAs. These RNAs do not code for protein but play critical catalytic and structural roles in many cellular processes including splicing and transcription (see ref. 9). SnRNA genes are compact and require relatively few sequence elements for correct expression, thus providing an ideal system to dissect the molecular mechanisms underlying transcription and transcript maturation.
We have already made significant progress in understanding the requirements for proper expression of these genes, which has, in turn, helped define general principles of gene expression control. For example, transcription and RNA processing must be coupled for production of both snRNAs and mRNAs by RNA polymerase II (see ref. 17). We have recently extended our studies to include the replication-activated histone genes which, like snRNA genes have no introns and have a specialized RNA 3' end formation signal.
Our latest findings indicate that elongation of transcription of short, intronless genes is controlled differently from elongation of transcription of longer intron-containing genes (ref. 10) and promises to afford insights into mechanisms required for expression of proto-oncogenes like c-myc and viruses like HIV that are controlled at the level of transcription elongation.
C. Laitem, J. Zaborowska, N.F. Isa, J. Kufs, M. Dienstbier, S. Murphy, 2015, CDK9 inhibitors define elongation checkpoints at both ends of RNA polymerase II-transcribed genes. Nat Struct Mol Biol. 22(5): 396-403.
S. Egloff, J. Zaborowska, C. Laitem, T. Kiss, S. Murphy, 2012, Ser7 phosphorylation of the CTD recruits the RPAP2 Ser5 phosphatase to snRNA genes. Mol Cell. 45(1): 111-22
S. Egloff, M. Dienstbier and S. Murphy, 2012, Updating the RNA polymerase CTD code: adding gene-specific layers. Trends Genet. 28: 333-41.
S. Egloff, D. O’Reilly, R. Chapman, A. Taylor, K Tanzhaus, L. Pitts, D. Eick and S. Murphy, 2007, Serine 7 of the RNA polymerase II CTD is specifically required for snRNA gene expression. Science 318: 1777-1780.