Dr Nick Watkins
- Email: email@example.com
- Telephone: +44 (0) 191 208 6991
- Address: Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne, NE2 4HH.
BSc. Hons Molecular Biology, University of Liverpool
Ph.D. U7 snRNP and histone gene expression, University of Liverpool
1997-2003 Postdoc. Max-Planck-Institut BPC, Göttingen, Germany.
1994-1997 Postdoc. North Carolina State University, Raleigh, USA.
Honours and Awards - Alexander von Humboldt Fellowship (1997 - 1999)
The Watkins lab is interested in the production of eukaryotic ribosomes. These large, RNA-protein complexes are responsible for the synthesis of all cellular protein. Regulating ribosome production therefore controls the rate of protein synthesis and this in turn determines how fast the cell can grow. Ribosome production is upregulated in almost all cancers. Our research falls into two basic areas:
1) Small nucleolar (sno)RNPs and ribosomal (r)RNA modification.
SnoRNPs are RNA-protein complexes that catalyse the post-transcriptional modification of rRNA. Defects in rRNA modification have been linked to the genetic disease Treacher-Collins syndrome. The modifications, the most common of which are 2'-O-methylation and pseudouridylation, are clustered around functionally important regions of the ribosome and are essential for efficient translation. The RNA component of the snoRNP selects the site of modification by base-pairing with the target site in the rRNA. These base-pairing interactions are also predicted to regulate the folding of the rRNA. We are interested in the mechanism by which the snoRNPs are recruited to the ribosomal RNA and how these complexes modulate rRNA folding and ribosome assembly.
Ribosome production is directly linked to the tumour suppressor proteins p53, p14-ARF and Rb and is regulated by the proto-oncogene c-Myc. The nucleolus is a major stress sensor in the cell, and disruption of its structure (as shown in the figure on the left) leads to p53 stabilisation. Most of the current knowledge about eukaryotic ribosome production is derived from studies in yeast and we are building on this by investigating the basic mechanism of ribosome synthesis, and its regulation, in human cells. We are particularly interested in how this process is controlled during cellular differentiation and transformation..
Current PhD students: Loren Macdonald, Andria Pelava
- BGM3035 - module leader
- Wells GR, Weichmann F, Sloan KE, Colvin D, Watkins NJ, Schneider C. The ribosome biogenesis factor yUtp23/hUTP23 coordinates key interactions in the yeast and human pre-40S particle and hUTP23 contains an essential PIN domain. Nucleic Acids Research 2017, 45(8), 4796-4809.
- Pelava A, Schneider C, Watkins NJ. The importance of ribosome production, and the 5S RNP–MDM2 pathway, in health and disease. Biochemical Society Transactions 2016, 44(4), 1086-1090.
- Wells GR, Weichmann F, Colvin D, Sloan KE, Kudla G, Tollervey D, Watkins NJ, Schneider C. The PIN domain endonuclease Utp24 cleaves pre-ribosomal RNA at two coupled sites in yeast and humans. Nucleic Acids Research 2016, 44(11), 5399-5409.
- Wells GR, Weichmann F, Colvin D, Sloan KE, Kudla G, Tollervey D, Watkins NJ, Schneider C. The PIN domain endonuclease Utp24 cleaves pre-ribosomal RNA at two coupled sites in yeast and humans (vol 44, pg 5399, 2016) [Corrigendum]. Nucleic Acids Research 2016, 44(18), 9016-9016.
- van Nues RW, Watkins NJ. Unusual C'/D' motifs enable box C/D snoRNPs to modify multiple sites in the same rRNA target region. Nucleic Acids Research 2016, (ePub ahead of Print).
- Leung E, Schneider C, Yan F, Mohi-El-Din H, Kudla G, Tuck A, Wlotzka W, Doronina VA, Bartley R, Watkins NJ, Tollervey D, Brown JD. Integrity of SRP RNA is ensured by La and the nuclear RNA quality control machinery. Nucleic Acids Research 2014, 42(16), 10698-10710.
- Sloan KE, Leisegang MS, Doebele C, Ramirez AS, Simm S, Safferthal C, Kretschmer J, Schorge T, Markoutsa S, Haag S, Karas M, Ebersberger I, Schleiff E, Watkins NJ, Bohnsack MT. The association of late-acting snoRNPs with human pre-ribosomal complexes requires the RNA helicase DDX21. Nucleic Acid Research 2014, 43(1), 553-564.
- Sloan KE, Bohnsack MT, Schneider C, Watkins NJ. The roles of SSU processome components and surveillance factors in the initial processing of human ribosomal RNA. RNA 2014, 20(4), 540-550.
- Sloan KE, Mattijssen S, Lebaron S, Tollervey D, Pruijn GJ, Watkins NJ. Both endonucleolytic and exonucleolytic cleavage mediate ITS1 removal during human ribosomal RNA processing. Journal of Cell Biology 2013, 200(5), 577-588.
- Sloan KE, Bohnsack MT, Watkins NJ. The 5S RNP couples p53 homeostasis to ribosome biogenesis and nucleolar stress. Cell Reports 2013, 5, 237-247.
- Sloan KE, Schneider C, Watkins NJ. Comparison of the yeast and human nuclear exosome complexes. Biochemical Society Transactions 2012, 40(4), 850-855.
- Turner AJ, Knox AA, Watkins NJ. Nucleolar disruption leads to the spatial separation of key 18S rRNA processing factors. RNA Biology 2012, 9(2), 175-186.
- Lebaron S, Schneider C, van Nues RW, Swiatkowska A, Walsh D, Böttcher B, Granneman G, Watkins NJ, Tollervey D. Proofreading of pre-40S ribosome maturation by a translation initiation factor and 60S subunits. Nature Structural & Molecular Biology 2012, 19(8), 744-753.
- Watkins NJ, Bohnsack MT. The box C/D and H/ACA snoRNPs: key players in the modification, processing and the dynamic folding of ribosomal RNA. Wiley Interdisciplinary Reviews: RNA 2012, 3(3), 397-414.
- Knox AA, McKeegan KS, Debieux CM, Traynor A, Richardson H, Watkins NJ. A weak C’ box renders U3 snoRNA levels dependent on hU3-55K binding. Molecular and Cellular Biology 2011, 31(12), 2404-2412.
- van Nues RW, Granneman S, Kudla G, Sloan KE, Chicken M, Tollervey D, Watkins NJ. Box C/D snoRNP catalysed methylation is aided by additional pre-rRNA base-pairing. EMBO Journal 2011, 30(12), 2420-2430.
- Maxwell S, Qu GS, Gagnon K, Biswas S, van-Nues R, Watkins N. Evolution of box C/D RNP structure and function. In: Experimental Biology Meeting 2011. 2011, Walter E Washington Convention Center, Washington, DC: Federation of American Societies for Experimental Biology.
- Qu G, van Nues RW, Watkins NJ, Maxwell ES. The Spatial-Functional Coupling of Box C/D and C'/D' RNPs Is an Evolutionarily Conserved Feature of the Eukaryotic Box C/D snoRNP Nucleotide Modification Complex. Molecular and Cellular Biology 2011, 31(2), 365-374.
- Ghalei H, Hsiao HH, Urlaub H, Wahl MC, Watkins NJ. A novel Nop5-sRNA interaction that is required for efficient archaeal box C/D sRNP formation. The RNA Journal 2010, 16(12), 2341-2348.
- Dean P, Scott JA, Knox AA, Quitard S, Watkins NJ, Kenny B. The Enteropathogenic E. coli Effector EspF Targets and Disrupts the Nucleolus by a Process Regulated by Mitochondrial Dysfunction. PLoS Pathogens 2010, 6(6), e1000961.
- Turner AJ, Knox AA, Prieto JL, McStay B, Watkins NJ. A Novel Small-Subunit Processome Assembly Intermediate That Contains the U3 snoRNP, Nucleolin, RRP5, and DBP4. Molecular and Cellular Biology 2009, 29(11), 3007-3017.
- McKeegan KS, Debieux CM, Watkins NJ. Evidence that the AAA+ Proteins TIP48 and TIP49 Bridge Interactions between 15.5K and the Related NOP56 and NOP58 Proteins during Box C/D snoRNP Biogenesis. Molecular and Cellular Biology 2009, 29(18), 4971-4981.
- Pessa HKJ, Will CL, Meng X, Schneider C, Watkins NJ, Perala N, Nymark M, Turunen JJ, Luhrmann R, Frilander MJ. Minor spliceosome components are predominantly localized in the nucleus. Proceedings of the National Academy of Sciences of the United States of America 2008, 105(25), 8655-8660.
- McKeegan KS, Debieux CM, Boulon S, Bertrand E, Watkins NJ. A dynamic scaffold of pre-snoRNP factors facilitates human box C/D snoRNP assembly. Molecular and Cellular Biology 2007, 27(19), 6782-6793.
- Lamb HK, Thompson P, Elliott C, Charles IG, Richards J, Lockyer M, Watkins N, Nichols C, Stammers DK, Bagshaw CR, Cooper A, Hawkins AR. Functional analysis of the GTPases EngA and YhbZ encoded by Salmonella typhimurium. Protein Science 2007, 16(11), 2391-2402.
- Watkins NJ, Lemm I, Luhrmann R. Involvement of nuclear import and export factors in U8 box C/D snoRNP biogenesis. Molecular and Cellular Biology 2007, 27(20), 7018-7027.
- Lemm I, Girard C, Kuhn AN, Watkins NJ, Schneider M, Bordonne R, Luhrmann R. Ongoing U snRNP biogenesis is required for the integrity of Cajal bodies. Molecular Biology of the Cell 2006, 17(7), 3221-3231.
- Schultz A, Nottrott S, Watkins NJ, Luhrmann R. Protein-protein and protein-RNA contacts both contribute to the 15.5K-mediated assembly of the U4/U6 snRNP and the box C/D snoRNPs. Molecular and Cellular Biology 2006, 26(13), 5146-5154.
- Watkins NJ, Lemm I, Ingelfinger D, Schneider C, Hoßbach M, Urlaub H, Lührmann R. Assembly and Maturation of the U3 snoRNP in the Nucleoplasm in a Large Dynamic Multiprotein Complex. Molecular Cell 2004, 16(5), 789-798.
- Granneman S, Vogelzangs J, Luhrmann R, Van Venrooij WJ, Pruijn GJM, Watkins NJ. Role of pre-rRNA base pairing and 80S complex formation in subnucleolar localization of the U3 snoRNP. Molecular and Cellular Biology 2004, 24(19), 8600-8610.
- Watkins NJ, Dickmanns A, Lührmann R. Conserved Stem II of the Box C/D Motif Is Essential for Nucleolar Localization and Is Required, Along with the 15.5K Protein, for the Hierarchical Assembly of the Box C/D snoRNP. Molecular and Cellular Biology 2002, 22(23), 8342-8352.
- Granneman S, Pruijn GJM, Horstman W, van Venrooij WJ, Lührmann R, Watkins NJ. The hU3-55K Protein Requires 15.5K Binding to the Box B/C Motif as Well as Flanking RNA Elements for Its Association with the U3 Small Nucleolar RNA in Vitro. Journal of Biological Chemistry 2002, 277(50), 48490-48500.
- Watkins NJ, Segault V, Charpentier B, Nottrott S, Fabrizio P, Bachi A, Wilm M, Rosbash M, Branlant C, Lührmann R. A common core RNP structure shared between the small nucleolar box C/D RNPs and the spliceosomal U4 snRNP. Cell 2000, 103(3), 457-466.
- N. J. Watkins,A. Gottschalk,G. Neubauer,B. Kastner,P. Fabrizio,M. Mann,R. Lührmann. Cbf5p, a potential pseudouridine synthase, and Nhp2p, a putative RNA- binding protein, are present together with Gar1p in all H BOX/ACA-motif snoRNPs and constitute a common bipartite structure. RNA 1998, 4(12), 1549-68.
- N. J. Watkins,D. R. Newman,J. F. Kuhn,E. S. Maxwell. In vitro assembly of the mouse U14 snoRNP core complex and identification of a 65-kDa box C/D-binding protein. RNA 1998, 4(5), 582-93.
- D. J. Leader,G. P. Clark,J. Boag,J. A. Watters,C. G. Simpson,N. J. Watkins,E. S. Maxwell,J. W. Brown. Processing of vertebrate box C/D small nucleolar RNAs in plant cells. Eur J Biochem 1998, 253(1), 154-60.
- L. Xia,N. J. Watkins,E. S. Maxwell. Identification of specific nucleotide sequences and structural elements required for intronic U14 snoRNA processing. RNA 1997, 3(1), 17-26.
- N. J. Watkins,R. D. Leverette,L. Xia,M. T. Andrews,E. S. Maxwell. Elements essential for processing intronic U14 snoRNA are located at the termini of the mature snoRNA sequence and include conserved nucleotide boxes C and D. RNA 1996, 2(2), 118-33.
- D. C. Boyd,P. C. Turner,N. J. Watkins,T. Gerster,S. Murphy. Functional redundancy of promoter elements ensures efficient transcription of the human 7SK gene in vivo. J Mol Biol 1995, 253(5), 677-90.
- N. J. Watkins,S. C. Phillips,P. C. Turner. The U7 small nuclear RNA genes of Xenopus borealis. Biochem Soc Trans 1992, 20(3), 301S.
- N. J. Watkins,S. C. Phillips,P. C. Turner. The Xenopus U7 snRNA-encoding gene has an unusually compact structure. Gene 1992, 120(2), 271-6.