Dr Claudia Schneider
Royal Society University Research Fellow
- Email: email@example.com
- Telephone: +44 (0) 191 208 7708
- Fax: +44 (0) 191 208 7424
- Address: Institute for Cell and Molecular Biosciences
The Medical School
University of Newcastle
Newcastle upon Tyne
Royal Society University Research Fellow
PhD on pre-mRNA splicing with Prof. Reinhard Lührmann (Philipps-University Marburg, Germany)
2004-2011 Postdoctoral research on RNA surveillance in budding yeast with Prof. David Tollervey (Wellcome Trust Centre for Cell Biology, University of Edinburgh). During this time I held independent Fellowships from the Human Frontier Science Program Organisation and the European Molecular Biology Organisation.
Honours and Awards
2011-2019 Royal Society University Research Fellowship (URF)
2005-2008 Human Frontier Science Program (HFSP) Long-Term Fellowship
2005 European Molecular Biology Organisation (EMBO) Long-Term Fellowship
2004 Prize for the best PhD at the Faculty of Medicine, Philipps-University Marburg
Quality control of coding and non-coding RNAs plays a vital role in assuring the fidelity of gene expression and overall fitness of all organisms. Specialised RNA surveillance systems, each employing a distinct network of ribonucleases and co-factors, detect and remove faulty RNA molecules. An important paradigm for mRNA quality control is the nonsense mediated decay (NMD) pathway, which prevents translation of potentially harmful truncated proteins from aberrant mRNAs. NMD has been linked to several genetic diseases and cancer.
In many cases it is unclear how target RNAs are recognised and degraded, and exonucleases were long believed to be the main players. However, this model was recently challenged by the identification of endonucleases containing PIN (PilT N-terminus) domains, which appear to play key roles in RNA surveillance in yeast and metazoans.
My laboratory is interested in the functions of novel PIN domain endonucleases in NMD and other surveillance pathways. During my postdoctoral work, I detected endonuclease activity in three PIN domain proteins in Saccharomyces cerevisiae; the exosome component Rrp44 (Schneider et al., 2009), the ribosome biogenesis factor Nob1 (Pertschy et al., 2009) and the mRNP quality control factor Swt1 (Skruzny et al., 2009). Five further PIN domain proteins are encoded in the genome of budding yeast: three largely uncharacterised proteins and two ribosome biogenesis factors.
Key to understand the roles of RNA surveillance factors is the identification of their substrates. We therefore apply in vivo crosslinking and high-throughput sequencing approaches (CRAC) to identify RNA binding sites of PIN domain proteins on a genome-wide scale. This will provide the starting points for biochemical, genetic and structural analyses.
- 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, epub ahead of print.
- Delan-Forino C, Schneider C, Tollervey D. Transcriptome-wide analysis of alternative routes for RNA substrates into the exosome complex. PLoS Genetics 2017, 13(3), e1006699.
- 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.
- 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.
- Schneider C, Tollervey D. Looking into the barrel of the RNA exosome. Nature Structural & Molecular Biology 2014, 21(1), 17-18.
- 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.
- Schneider C, Tollervey D. Threading the barrel of the RNA exosome. Trends in Biochemical Sciences 2013, 38(10), 485-493.
- Sloan KE, Schneider C, Watkins NJ. Comparison of the yeast and human nuclear exosome complexes. Biochemical Society Transactions 2012, 40(4), 850-855.
- 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.
- Schneider C, Kudla G, Wlotzka W, Tuck A, Tollervey D. Transcriptome-wide Analysis of Exosome Targets. Molecular Cell 2012, 48(3), 422-433.
- Skružný M, Schneider C, Rácz A, Weng J, Tollervey D, Hurt E. An endoribonuclease functionally linked to perinuclear mRNP quality control associates with the nuclear pore complexes. PLoS Biology 2009, 7(1), e1000008.
- Pertschy B, Schneider C, Gnädig M, Schäfer T, Tollervey D, Hurt E. RNA helicase Prp43 and its co-factor Pfa1 promote 20S to 18S rRNA processing catalyzed by the endonuclease Nob1. Journal of Biological Chemistry 2009, 284(50), 35079-35091.
- Schneider C, Leung E, Brown J, Tollervey D. The N-terminal PIN domain of the exosome subunit Rrp44 harbors endonuclease activity and tethers Rrp44 to the yeast core exosome. Nucleic Acids Research 2009, 37(4), 1127-1140.
- 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.
- Schneider C, Anderson JT, Tollervey D. The exosome subunit Rrp44 plays a direct role in RNA substrate recognition. Molecular Cell 2007, 27(2), 324-331.
- 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.
- Schneider C, Will CL, Brosius J, Frilander MJ, Lührmann R. Identification of an evolutionarily divergent U11 small nuclear ribonucleoprotein particle in Drosophila. Proceedings of the National Academy of Sciences 2004, 101(26), 9584-9589.
- Will CL, Schneider C, Hossbach M, Urlaub H, Rauhut R, Elbashir S, Tuschl T, Lührmann R. The human 18S U11/U12 snRNP contains a set of novel proteins not found in the U2-dependent spliceosome. RNA 2004, 10(6), 929-941.
- Schneider C, Will CL, Makarova OV, Makarov EM, Lührmann R. Human U4/U6.U5 and U4atac/U6atac.U5 tri-snRNPs exhibit similar protein compositions. Molecular and Cellular Biology 2002, 22(10), 3219-3229.
- Will CL, Schneider C, MacMillan AM, Katopodis NF, Neubauer G, Wilm M, Lührmann R, Query CC. A novel U2 and U11/U12 snRNP protein that associates with the pre-mRNA branch site. EMBO Journal 2001, 20(16), 4536-4546.
- Will CL, Schneider C, Reed R, Lührmann R. Identification of both shared and distinct proteins in the major and minor spliceosomes. Science 1999, 284(2003), 2003-2005.