Biochemistry; Gene Expression Regulation; Molecular Biology
- Epigenetics & RNA Biology/RNA Methylation Lab
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
- Affects innate immunity processes
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.
- Schaefer, M. et al., 2010. RNA methylation by Dnmt2 protects transfer RNAs against stress-induced cleavage. Genes & Development, 24(15), pp.1590-1595. Available at: http://dx.doi.org/10.1101/gad.586710.
- Schaefer, M. et al., 2008. RNA cytosine methylation analysis by bisulfite sequencing. Nucleic Acids Research, 37(2), pp.e12-e12. Available at: http://dx.doi.org/10.1093/nar/gkn954.
- Schaefer, M. et al., 2009. Azacytidine Inhibits RNA Methylation at DNMT2 Target Sites in Human Cancer Cell Lines. Cancer Research, 69(20), pp.8127-8132. Available at: http://dx.doi.org/10.1158/0008-5472.CAN-09-0458.
- Tuorto, F. et al., 2012. RNA cytosine methylation by Dnmt2 and NSun2 promotes tRNA stability and protein synthesis. Nature Structural & Molecular Biology, 19(9), pp.900-905. Available at: http://dx.doi.org/10.1038/nsmb.2357.
- Durdevic, Z. et al., 2013. The RNA Methyltransferase Dnmt2 Is Required for Efficient Dicer-2-Dependent siRNA Pathway Activity in Drosophila. Cell Reports, 4(5), pp.931-937. Available at: http://dx.doi.org/10.1016/j.celrep.2013.07.046.