Detail

Keywords

Biochemistry; Gene Expression Regulation; Molecular Biology

Research group(s)

• Epigenetics & RNA Biology / RNA Methylation Lab
  Research Area: Our group aims to understand the biology of RNA modification enzymes that attach methyl groups (forming m5C) and the impact of m5C groups in RNA on cell biology.
  Members:
  Matthias R. Schaefer

Research interests

RNA Modifications: Their Impact on Stress Responses, Gene Expression And Innate Immunity

It is well established that DNA and protein modifications influence gene expression. Importantly, studies on DNA modifications (i.e. cytosine-methylation and its derivatives) and particular protein modifications (i.e. histone modifications) contributed greatly to the concept of epigenetic regulation of gene expression. Recent findings point towards a role for RNA modifiations in gene expression regulation. This has set the stage for proposing a new and exciting concept: RNA epigenetics. 

RNA molecules carry more than 130 distinct post-transcriptional modifications. Although some of these modifications influence RNA maturation and stability, the biological function of most RNA modifications remains completely unclear.

My group applies genetic and biochemical tools to understand the biological systems that place, interprete, and erase a particular RNA modification (5-methylcytosine, m⁵C). In particular, we are interested as to how m⁵C

• Impacts on RNA stability and function
• Controls stress-induced RNA processing
• Contributes to the regulation of gene expression during stress responses

Our long-term goal is to characterize how m⁵C and other RNA modifications contribute to genome regulation and, importantly, how they could influence the re-programming of gene expression between generations in response to environmental changes.

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.

Grants

• RNA-DECO: "Decorating RNA for a Purpose" (2020)
  Source of Funding: FWF (Austrian Science Fund), Special Research Programmes (SFB F80)
  Principal Investigator
• Biological function of m5C RNA methylation in Drosophila (2016)
  Source of Funding: FWF (Austrian Science Fund), Stand-Alone Project
  Principal Investigator

Selected publications

1. 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.
2. Drino, A. & 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.
3. 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.
4. Jantsch, M.F. et al., 2018. Positioning Europe for the EPITRANSCRIPTOMICS challenge. RNA Biology, pp.1-3. Available at: http://dx.doi.org/10.1080/15476286.2018.1460996.
5. Schaefer, M., Kapoor, U. & Jantsch, M.F., 2017. Understanding RNA modifications: the promises and technological bottlenecks of the �epitranscriptome.� Open Biology, 7(5), p.170077. Available at: http://dx.doi.org/10.1098/rsob.170077.