Staff Profile

Qualifications

PhD in Biochemistry with Prof. Reinhard Lührmann (Philipps-University Marburg, Germany)

Previous Positions

Royal Society University Research Fellow (2011-2019)

Postdoctoral research 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.

Memberships

RNA Society, Biochemical Society

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, Germany

Research

Research Interests

Messenger RNAs (mRNAs) are the blueprints for protein production, but other types of RNA also drive and modulate all aspects of gene expression. In eukaryotic cells, RNA is never made “ready to use“, and the generation of functional molecules requires a sophisticated network of ribonucleases and co-factors that can mature the RNA. Ribonucleases are also important players in (m)RNA quality control networks, which monitor RNA processing pathways, maintain accurate RNA levels, and recognise and remove faulty molecules.

In many cases it is unclear how target RNAs are recognised and either processed or degraded, and exonucleases were long believed to be the main players. However, this view was challenged by the identification of a group of endonucleases containing PIN (PilT N-terminus) domains, which play key roles in RNA processing and quality control.

We are particularly interested in PIN domain endonucleases involved in RNA maturation, which often requires multiple processing steps. The assembly of ribosomes, large RNA-protein (RNP) machineries that synthesise all cellular proteins, is the major consumer of cellular energy and by far the most complex RNA processing pathway. Ribosome biogenesis determines the proliferative rate of cells and defects are linked to human diseases (“ribosomopathies”) and cancer. Key events in ribosomal RNA (rRNA) processing are endonucleolytic cleavages that release mature rRNAs from a large precursor transcript. Here, three PIN domain proteins are required for several RNA cleavage events. Using a combination of in vitro and in vivo approaches, we aim to characterise the roles of these PIN domain proteins and the timely and spatial regulation of their activity in budding yeast (Saccharomyces cerevisiae) and human cells.

Using budding yeast, we also study the role of a putative PIN domain endonuclease in the nonsense-mediated decay (NMD) messenger (m)RNA surveillance pathway, which degrades faulty mRNAs that could be translated into toxic proteins. Defects in the NMD pathway are linked to ~30% of all inherited human diseases (e.g. Duchenne muscular dystrophy) and cancer. This project also examines the intriguing, but not well understood link between mRNA quality control and genome stability.

Characterising fundamental, evolutionarily conserved processes such as ribosome biogenesis and RNA quality control in two eukaryotic systems offers a strong basis to clarify underlying mechanisms of genetic diseases, cancer and ageing, and will therefore enable the identification of new therapeutic targets.

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Teaching

Primary and co-supervision as well as marking of PhD, MRes and Undergraduate Final Year Projects (Module CMB3000)

Contribution to MRes Module MMB8008 ("Chromosome Biology and Cell Cycle Control in Health and Disease")

Contribution to Undergraduate Modules BGM3063 (“Biochemistry of Gene Expression”) and BGM3055 (“RNA genetic disease and development”)

Active member of PhD progression panels and the tutor-tutee mentoring program for UG and PG students and Post Docs at Newcastle University

Publications

Aquino GRR, Krogh N, Hackert P, Martin R, Gallesio JD, van Nues RW, Schneider C, Watkins NJ, Nielsen H, Bohnsack KE, Bohnsack MT. RNA helicase-mediated regulation of snoRNP dynamics on pre-ribosomes and rRNA 2'-O-methylation. Nucleic Acids Research 2021, 49(7), 4066-4084.
Muller JS, Burns DT, Griffin H, Wells GR, Zendah RA, Munro B, Schneider C, Horvath R. RNA exosome mutations in pontocerebellar hypoplasia alter ribosome biogenesis and p53 levels. Life Science Alliance 2020, 3(8), e202000678.
Sloan KE, Knox AA, Wells GR, Schneider C, Watkins NJ. Interactions and activities of factors involved in the late stages of human 18S rRNA maturation. RNA Biology 2019, 16(2), 196-210.
Choque E, Schneider C, Gadal O, Dez C. Turnover of aberrant pre-40S pre-ribosomal particles is initiated by a novel endonucleolytic decay pathway. Nucleic Acids Research 2018, 46(9), 4699-4714.
Delan-Forino C, Schneider C, Tollervey D. RNA substrate length as an indicator of exosome interactions in vivo. Wellcome Open Research 2017, 2, 34.
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.
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.

Dr Claudia Schneider

Principal Research Associate