Dr Phil Mitchell
Tel: 0114 222 2821
Building on the discovery and characterisation of the exosome ribonuclease complex (Mitchell et al., 1997; Allmang et al., 1999), my lab’s research addresses the molecular mechanisms of RNA quality control in eukaryotic cells.
Counter-intuitively, much of the RNA that a eukaryotic cell produces is rapidly degraded after being transcribed. This widespread turnover reflects highly active RNA quality control systems and the widespread transcription and degradation of unstable noncoding RNAs, as well as the processing of functional RNA from much longer precursors. Key to many of these processes is the exosome ribonuclease (RNase) complex. Mutations within genes of the exosome directly underlie forms of neurodegenerative disease and autoimmunity and are also associated with multiple myeloma. We are interested in understanding how RNases recognise their substrates, how the activities of these enzymes are regulated, and how they impact on human health and disease. We use a range of complementary experimental techniques, including cellular RNA analyses, molecular genetics, protein biochemistry, cell imaging and in vitro RNA degradation assays. Our current research aims include determining the importance of the different substrate pathways that exist through the exosome complex, understanding the functional redundancy between the exosome and Rex1 RNases, and defining the molecular interactions that are mediated through eukaryotic proteins containing the C1D domain, which is exemplified by the exosome subunit Rrp47.
RNA, gene expression, ribonuclease, exosome, quality control
Level 4 Modules
MBB405 Advanced Research Topics (Module Coordinator)
Level 3 Modules
MBB325 The RNA World
Level 2 Modules
MBB267 Genes, Genomes and Chromosomes (Module Coordinator)
Level 1 Modules
MBB164 Molecular Biology (Module Coordinator)
Honours and Distinctions
- Schuch B, Feigenbutz M, Makino DL, Falk S, Basquin C, Mitchell P & Conti E (2014) The exosome-binding factors Rrp6 and Rrp47 form a composite surface for recruiting the Mtr4 helicase.. EMBO Journal, 33(23), 2829-2846. View this article in WRRO
- Mitchell P (2014) Exosome substrate targeting: the long and short of it. Biochemical Society Transactions, 42(4), 1129-1134. View this article in WRRO
- Feigenbutz M, Garland W, Turner M & Mitchell PJ (2013) The exosome cofactor Rrp47 is critical for the stability and normal expression of its associated exoribonuclease Rrp6 in Saccharomyces cerevisiae. PLOS One. View this article in WRRO
- Garland W, Feigenbutz M, Turner M & Mitchell P (2013) Rrp47 functions in RNA surveillance and stable RNA processing when divorced from the exoribonuclease and exosome-binding domains of Rrp6.. RNA, 19(12), 1659-1668.
- Feigenbutz M, Jones R, Besong TMD, Harding SE & Mitchell P (2013) Assembly of the yeast exoribonuclease Rrp6 with its associated cofactor Rrp47 occurs in the nucleus and is critical for the controlled expression of Rrp47.. J Biol Chem, 288(22), 15959-15970.
- Costello JL, Stead JA, Feigenbutz M, Jones RM & Mitchell P (2011) The C-terminal region of the exosome-associated protein Rrp47 is specifically required for box C/D small nucleolar RNA 3'-maturation.. J Biol Chem, 286(6), 4535-4543.
- Mitchell P & Tollervey D (2011) Finding the exosome.. Adv Exp Med Biol, 702, 1-8.
- Mitchell P (2010) Rrp47 and the function of the Sas10/C1D domain.. Biochem Soc Trans, 38(4), 1088-1092. View this article in WRRO
- Butler JS & Mitchell P (2010) Rrp6, Rrp47 and Cofactors of the Nuclear Exosome. Advances in Experimental Medicine and Biology, 702, 91-104.
- Stead JA, Costello JL, Livingstone MJ & Mitchell P (2007) The PMC2NT domain of the catalytic exosome subunit Rrp6p provides the interface for binding with its cofactor Rrp47p, a nucleic acid-binding protein.. Nucleic Acids Res, 35(16), 5556-5567. View this article in WRRO