Sheffield Institute for Nucleic Acids

Dr Phil Mitchell

Research Interests

Dr Mitchell has over 25 years of research experience in the field of gene expression, spanning work on the architecture of ribosomes and ribosome complexes, and the analysis of cellular RNA processing and degradation pathways.  Since characterising the exosome ribonuclease complex, which has a pivotal role in the production and/or degradation of most RNA transcripts in eukaryotic cells, Dr Mitchell’s research has been largely focused on how it functions together with associated complexes such as the TRAMP RNA helicase/poly(A) polymerase complex.  The importance of exosome function in human health is reflected by the correlation between active site mutations within the catalytic subunit Rrp44 and the incidence of multiple myeloma and acute myeloid leukemia, while mutations within structural subunits have been linked to a number of neurological disorders.

Research highlights include the determination of the three-dimensional arrangement of 23S rRNA within the ribosome, mapping contacts between the small and large ribosome subunits, the characterisation and functional analysis of the exosome complex, and the analysis of a principal molecular contact between the exosome and TRAMP complexes.


Publications

  • Mitchell, P. (2014) Exosome targeting: the long and short of it. Biochem Soc Trans 42, 1129-1134.
  • Schuch, B., Feigenbutz, M., Makino, D.L., Falk, S. Basquin, C., Mitchell, P. and Conti, E. (2014) The exosome binding factors Rrp6 and Rrp47 form a composite surface for recruiting the Mtr4 helicase. EMBO J. 33, 2829-2846.
  • Feigenbutz, M., Garland, W., Turner, M. and Mitchell, P. (2013) The exosome cofactor Rrp47 is critical for the stability and normal expression of its associated exoribonuclease Rrp6 in Saccharomyces cerevisiae. PLoS ONE 8, e80752.
  • Garland, W., Feigenbutz, M., Turner, M. and 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, 1659-1668.
  • Feigenbutz, M., Jones, R., Besong, T.M.D., Harding, S.E. and 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, 15959-15970.
  • Costello, J. L., Stead, J. A., Feigenbutz, M., Jones, R. M. & 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, 4535-4543.
  • Mitchell, P. (2010). Rrp47 and the function of the Sas10/C1D domain. Biochem Soc Trans 38, 1088-1092.
  • Butler, J. S. & Mitchell, P. (2010). Rrp6, Rrp47 and Cofactors of the Nuclear Exosome. Advances in Experimental Medicine and Biology 702, 91-104.
  • Mitchell, P. & Tollervey, D. (2010). Finding the exosome. Advances in Experimental Medicine and Biology 702, 1-8.
  • Stead, J. A., Costello, J. L., Livingstone, M. J. & 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, 5556-5567.
Dr Phil Mitchell
Lecturer
Department of Molecular Biology and Biotechnology
+44 (0)114 222 2821
p.j.mitchell@sheffield.ac.uk