MicroRNA Regulation of Gene Expression

Dr Martin Bushell

MRC Senior Fellow

MRC Toxicology Unit
Hodgkin Building
PO Box 138
University of Leicester
Lancaster Road, Leicester
LE1 9HN, UK

Tel: +44 (0)116 252 5568
Email: Send Email

Academic Appointments

2010-Present MRC Senior Fellow, MRC Toxicology Unit
2005-2009 BBSRC David Phillips Fellow, University of Nottingham
2002-2004 Wellcome Travelling Fellow with Professor Anne Willis, Leicester, UK
2000-2002 Wellcome Travelling Fellow with Professor Peter Sarnow, Stanford, USA
1999-2000 Research Fellow with Professor Mike Clemens
D.Phil University of Sussex, with Dr. Simon Morley

Publications List

Meijer HA, Kong YW, Lu WT, Wilczynska A, Spriggs RV, Robinson SW, Godfrey JD, Willis AE, Bushell M.  Translational repression and eIF2A2 activity are critical for microRNA-mediated gene regulation.  Science, 2013 5 April: Vol. 340 no. 6128 pp. 82-85 DOI: 10.1126/science.1231197

Kong YW, Ferland-McCollough D, Jackson TJ, Bushell M.  MicroRNAs in cancer management. Lancet Oncol. 2012 Jun;13(6):e249-58.

Moreno JA, Radford H, Peretti D, Steinert JR, Verity N, Martin MG, Halliday M, Morgan J, Dinsdale D, Ortori CA, Barrett DA, Tsaytler P, Bertolotti A, Willis AE, Bushell M, Mallucci GR.  Sustained translational repression by eIF2α-P mediates prion neurodegeneration. Nature, 2012 May 6;485(7399):507-11

Ferland-McCollough D, Fernandez-Twinn D, Cannell IG, Warner M, Vaag AA, Bork-Jensen J, Brøns C, Gant TW, Willis AE, Siddle K, Bushell M, Ozanne SE. Programming of adipose tissue miR-483-3p and GDF-3 expression by maternal diet in type 2 diabetes. Cell Death and Differentiation, 2012 Jun;19(6):1003-12

Kress TR, Cannell IG, Brenkman AB, Samans B, Gaestel M, Roepman P, Burgering BM, Bushell M, Rosenwald A, Eilers M. The MK5/PRAK kinase and Myc form a negative feedback loop that is disrupted during colorectal tumorigenesis. Mol Cell. 2011 Feb 18; 41(4):445-57.

Ferland-McCollough D, Ozanne SE, Siddle K, Willis AE, Bushell M. The involvement of microRNAs in Type 2 diabetes. Biochem Soc Trans. 2010 38(6):1565-70.

Spriggs KA, Bushell M, Willis AE.  Translational regulation of gene expression during conditions of cell stress. Mol Cell. 2010 40(2):228-37

James V, Zhang Y, Foxler D, de Moor C, Kong YW , Webb T, Self T, Feng Y, Lagos D, Chu CY, Rana T, Morley S, Gregory L, Bushell M, Sharp T. LIM-domain proteins, LIMD1, Ajuba, and WTIP are required for microRNA-mediated gene silencing. 2010, Proc Natl Acad Sci U S A. 2010 107:12499-504.

Lou JJ, Chua YL, Chew EH, Gao J, Bushell M, Hagen T. Inhibition of hypoxia-inducible factor-1alpha (HIF-1alpha) protein synthesis by DNA damage inducing agents. PLoS One. 2010 May 7;5(5):e10522.

Cannell IG, Bushell M. Regulation of Myc by miR-34c: A mechanism to prevent genomic instability? 2010, Cell Cycle, 2010; 9(14).

Cannell IG, Kong YW, Johnston SJ, Chen ML, Dobbyn HC, Collins HM, Elia A, Kress T, Dickens M, Clemens MJ, Heery DM, Eilers M, Willis AE, Bushell M. p38 MAPK/MK2-mediated induction of miR-34c following DNA damage prevents Myc-dependent DNA replication. Proc Natl Acad Sci U S A. 2010 107:5375-80.

Cobbold LC, Wilson LA, Sawicka K, King HA, Kondrashov AV, Spriggs KA, Bushell M, Willis AE. Up-regulated c-myc expression in multiple myeloma via internal ribosome entry results from increased expression of PTB-1 and YB1. Oncogene.  2010 May 13;29(19):2884-91

Garrey JL, Lee YY, Au HH, Bushell M, Jan E. Host and viral translational mechanisms during Cricket paralysis virus infection. J Virol. 2009 Nov 4.

Le Quesne JP, Spriggs KA, Bushell M, Willis AE. Dysregulation of protein synthesis and disease. J Pathol. 2009 Oct 13.

Kondrashov AV, Spriggs KA, Bushell M, Willis AE. Co-ordinated regulation of translation following DNA damage. Cell Cycle. 2009, 8(19):3067-8

Spriggs KA, Cobbold LC, Ridley SH, Coldwell M, Bottley A, Bushell M, Willis AE, Siddle K. The human insulin receptor mRNA contains a functional internal ribosome entry segment. Nucleic Acids Res. 2009 Aug 4.

Powley IR, Kondrashov A, Young LA, Dobbyn HC, Hill K, Cannell IG, Stoneley M, Kong YW, Cotes JA, Smith GM, Wek R, Hayes C, Gant TW, Spriggs KA, Bushell M, Willis AE. Translational re-programming following UVB irradiation is mediated by DNA-PKcs and allows selective recruitment to the polysomes of mRNAs encoding DNA repair enzymes. Genes Dev. 2009 23:1207.

Spriggs KA, Cobbold LC, Jopling CL, Cooper R, Wilson LA, Stoneley M, Coldwell MJ, Poncet D, Shen YC, Morley SJ, Bushell M, Willis AE. Canonical initiation factor requirements of the Myc family of internal ribosome entry segments. Mol Cell Biol. 2009 6:1565-74.

Cannell IG, Kong YW, Bushell M. How do microRNAs regulate gene expression? Biochem Soc Trans. 2008 36:1224-31. Review.

Sawicka K, Bushell M, Spriggs KA, Willis AE. Polypyrimidine-tract-binding protein: a multifunctional RNA-binding protein. Biochem Soc Trans. 2008 36:641-7. Review.

Kong YW, Cannell IG, de Moor CH, Hill K, Garside PG, Hamilton TL, Meijer HA, Dobbyn HC, Stoneley M, Spriggs KA, Willis AE, Bushell M. The mechanism of micro-RNA-mediated translation repression is determined by the promoter of the target gene. Proc Natl Acad Sci U S A. 2008 105:8866-71.

Bushell M, Stoneley M, Spriggs KA, Willis AE. SF2/ASF TORCs up translation. Mol Cell. 2008 30:262-3.

Grabowska AM, Berry CA, Hughes J, Bushell M, Willis AE, Watson SA. A gastrin transcript expressed in gastrointestinal cancer cells contains an internal ribosome entry site. Br J Cancer. 2008 ;98:1696-703.

Spriggs KA, Stoneley M, Bushell M, Willis AE. Re-programming of translation following cell stress allows IRES-mediated translation to predominate. Biol Cell. 2008 100:27-38. Review.

Cobbold LC, Spriggs KA, Haines SJ, Dobbyn HC, Hayes C, de Moor CH, Lilley KS, Bushell M, Willis AE. Identification of internal ribosome entry segment (IRES)-trans-acting factors for the Myc family of IRESs. Mol Cell Biol. 2008 28:40-9.

Dobbyn HC, Hill K, Hamilton TL, Spriggs KA, Pickering BM, Coldwell MJ, de Moor CH, Bushell M, Willis AE. Regulation of BAG-1 IRES-mediated translation following chemotoxic stress. Oncogene. 2008 27:1167-74.

Meijer HA, Bushell M, Hill K, Gant TW, Willis AE, Jones P, de Moor CH. A novel method for poly(A) fractionation reveals a large population of mRNAs with a short poly(A) tail in mammalian cells. Nucleic Acids Res. 2007; 35(19):e132.

Bushell M, Stoneley M, Kong YW, Hamilton TL, Spriggs KA, Dobbyn HC, Qin X, Sarnow P, Willis AE. Polypyrimidine tract binding protein regulates IRES-mediated gene expression during apoptosis. Mol Cell. 2006 23:401-12.

Hamilton TL, Stoneley M, Spriggs KA, Bushell M. TOPs and their regulation. Biochem Soc Trans. 2006 34:12-6. Review.

Mitchell SA, Spriggs KA, Bushell M, Evans JR, Stoneley M, Le Quesne JP, Spriggs RV, Willis AE. Identification of a motif that mediates polypyrimidine tract-binding protein-dependent internal ribosome entry. Genes Dev. 2005 19:1556-71.

Spriggs KA, Bushell M, Mitchell SA, Willis AE. Internal ribosome entry segment-mediated translation during apoptosis: the role of IRES-trans-acting factors. Cell Death Differ. 2005 12:585-91. Review.

Bushell M, Stoneley M, Sarnow P, Willis AE. Translation inhibition during the induction of apoptosis: RNA or protein degradation? Biochem Soc Trans. 2004  32:606-10.

Fraser CS, Lee JY, Mayeur GL, Bushell M, Doudna JA, Hershey JW. The j-subunit of human translation initiation factor eIF3 is required for the stable binding of eIF3 and its subcomplexes to 40 S ribosomal subunits in vitro. J Biol Chem. 2004 279:8946-56.

Constantinou C, Bushell M, Jeffrey IW, Tilleray V, West M, Frost V, Hensold J, Clemens MJ. p53-induced inhibition of protein synthesis is independent of apoptosis. Eur J Biochem. 2003 270:3122-32.

Bushell M, Sarnow P. Hijacking the translation apparatus by RNA viruses. J Cell Biol. 2002 158(3):395-9. Review.

Horton LE, Bushell M, Barth-Baus D, Tilleray VJ, Clemens MJ, Hensold JO. p53 activation results in rapid dephosphorylation of the eIF4E-binding protein 4E-BP1, inhibition of ribosomal protein S6 kinase and inhibition of translation initiation. Oncogene. 2002 21:5325-34.

Jeffrey IW, Bushell M, Tilleray VJ, Morley S, Clemens MJ. Inhibition of protein synthesis in apoptosis: differential requirements by the tumor necrosis factor alpha family and a DNA-damaging agent for caspases and the double-stranded RNA-dependent protein kinase. Cancer Res. 2002 62:2272-80.

Bushell M, Wood W, Carpenter G, Pain VM, Morley SJ, Clemens MJ. Disruption of the interaction of mammalian protein synthesis eukaryotic initiation factor 4B with the poly(A)-binding protein by caspase- and viral protease-mediated cleavages. J Biol Chem. 2001 276:23922-8.

Morley SJ, Jeffrey I, Bushell M, Pain VM, Clemens MJ. Differential requirements for caspase-8 activity in the mechanism of phosphorylation of eIF2alpha, cleavage of eIF4GI and signaling events associated with the inhibition of protein synthesis in apoptotic Jurkat T cells. FEBS Lett. 2000 477:229-36.

Bushell M, Poncet D, Marissen WE, Flotow H, Lloyd RE, Clemens MJ, Morley SJ. Cleavage of polypeptide chain initiation factor eIF4GI during apoptosis in lymphoma cells: characterisation of an internal fragment generated by caspase-3-mediated cleavage. Cell Death Differ. 2000 7:628-36.

Clemens MJ, Bushell M, Jeffrey IW, Pain VM, Morley SJ. Translation initiation factor modifications and the regulation of protein synthesis in apoptotic cells. Cell Death Differ. 2000 7:603-15. Review.

Bushell M, Wood W, Clemens MJ, Morley SJ. Changes in integrity and association of eukaryotic protein synthesis initiation factors during apoptosis. Eur J Biochem. 2000 267:1083-91.

Bushell M, McKendrick L, Jänicke RU, Clemens MJ, Morley SJ. Caspase-3 is necessary and sufficient for cleavage of protein synthesis eukaryotic initiation factor 4G during apoptosis. FEBS Lett. 1999 451:332-6.

Clemens MJ, Bushell M, Morley SJ. Degradation of eukaryotic polypeptide chain initiation factor (eIF) 4G in response to induction of apoptosis in human lymphoma cell lines. Oncogene. 1998 17:2921-31.

Morley SJ, McKendrick L, Bushell M. Cleavage of translation initiation factor 4G (eIF4G) during anti-Fas IgM-induced apoptosis does not require signalling through the p38 mitogen-activated protein (MAP) kinase. FEBS Lett. 1998 438:41-8.