Biochemistry; Gene Expression Regulation; Molecular Biology
- tRNA modifications & tRNA-derived small RNAs
Head: Matthias R. Schaefer
Research Area: The exact biological function of most RNA modifications remains unclear. My research group focuses on the biological function of specific tRNA modifications. We apply genetic and biochemical tools using both mammalian cell culture and model organisms to understand how the activities and interactions of particular RNA methylation systems impact on: 1) tRNA stability and stress-induced tRNA processing into tsRNAs; 2) tRNA and tsRNA interactions with RNA-binding proteins.
Our group aims at understanding how enzymes that attach m5C to RNA impact the biological function of tRNAs. Our long-term goal is to characterize how m5C contributes to the regulation of gene expression and, importantly, how m5C in RNA influences the re-programming of gene expression during stress conditions.
We apply genetic and biochemical tools to human cells and the model organism Drosophila to systematically study (cytosine-5) RNA methylation systems.
Specifically, we aim to understand how m5C:
+ Controls stress-induced tRNA processing
+ Affects the interaction with RNA-binding proteins
+ Contributes to the regulation of gene expression
Techniques, methods & infrastructure
We employ human cell culture models and the genetically tractable model organism Drosophila melanogaster and various stress paradigms to understand the function of m5C in RNA.
CRISPR/Cas9-mediated genomic editing and a wide range of molecular biology, biochemistry and RNA biology techniques are well established in the lab.
(Cytosine-5) RNA methylation mapping at single nucleotide level using RNA bisulfite sequencing in high-throughput format is routinely used in the lab.
- 'Preserving the Immunological Memory of Previous Generations' (2023)
Source of Funding: Medical University of Vienna, FWF, 1000-Ideas Grant (TAI 842)
- Determining the function of tRNA fragment binding to specific metabolic enzymes (2023)
Source of Funding: Medical University of Vienna, FWF, doc.funds, 'RNA@Core, Molecular mechanisms in RNA Biology'
- 'Biochemical dissection of tRNA fragment biogenesis' (2022)
Source of Funding: Medical University of Vienna, FWF, stand-alone (P 35489)
- RNA-DECO: "Decorating RNA for a Purpose" (2020)
Source of Funding: FWF (Austrian Science Fund), Special Research Programmes (SFB F80)
- Biological function of m5C RNA methylation in Drosophila (2016)
Source of Funding: FWF (Austrian Science Fund), Stand-Alone Project
- Drino, A. et al. (2023) ‘Identification of RNA helicases with unwinding activity on angiogenin-processed tRNAs’, Nucleic Acids Research, 51(3), pp. 1326–1352. Available at: http://dx.doi.org/10.1093/nar/gkad033.
- Sanadgol, N. et al. (2022) ‘Experimental paradigms revisited: oxidative stress-induced tRNA fragmentation does not correlate with stress granule formation but is associated with delayed cell death’, Nucleic Acids Research, 50(12), pp. 6919–6937. Available at: http://dx.doi.org/10.1093/nar/gkac495.
- Drino, A. et al. (2020) ‘Production and purification of endogenously modified tRNA-derived small RNAs’, RNA Biology, 17(8), pp. 1104–1115. Available at: http://dx.doi.org/10.1080/15476286.2020.1733798.
- Drino, A. and Schaefer, M.R. (2018) ‘RNAs, Phase Separation, and Membrane-Less Organelles: Are Post-Transcriptional Modifications Modulating Organelle Dynamics?’, BioEssays, 40(12), p. 1800085. Available at: http://dx.doi.org/10.1002/bies.201800085.
- Genenncher, B. et al. (2018) ‘Mutations in Cytosine-5 tRNA Methyltransferases Impact Mobile Element Expression and Genome Stability at Specific DNA Repeats’, Cell Reports, 22(7), pp. 1861–1874. Available at: http://dx.doi.org/10.1016/j.celrep.2018.01.061.