Mechanisms Regulating Gene Expression

Division of Mechanisms Regulating Gene Expression

Prof. Dr. Michaela Frye

Skin explant cell culture
© dkfz.de

The decision of stem cells to self-renew, proliferate or undergo differentiation is initiated by external stimuli that are linked to an intrinsic network of transcriptional, post-transcriptional and translational processes. RNA plays versatile roles in the transcription and translation of genes into proteins. To expand the function of an RNA molecule and to increase its capacity to encode information, each nucleobase can be chemically modified. To date over 150 chemical modifications are known in RNA. Many RNA modifications are functionally indispensable for protein translation because they regulate messenger RNA stability and splicing as well as protein translation efficiency and accuracy.
One of the most common chemical RNA modification is methylation. Cytosine-5 RNA methylation for instance, is mediated by a large group of evolutionary conserved enzymes. The correct deposition of a methyl mark at cytosines is required for normal development and aberrant RNA methylation can lead to severe human diseases. Using a combination of novel transcriptome-wide quantitative analyses and well-established mouse and human in vitro and in vivo differentiation models, our group dissects the roles of RNA methyltransferases and their methylated target RNAs in normal development, human disease and cancer.

Ultimately, this division seeks to understand how RNA modification pathways regulate stem cell fate, and to explore whether modulation of RNA-modification pathways can help to protect from cancer.

Contact

Prof. Dr. Michaela Frye
Mechanisms Regulating Gene Expression (A350)
Deutsches Krebsforschungszentrum
Im Neuenheimer Feld 280
69120 Heidelberg
Tel: +49 6221 42 4165

Selected Publications

  • Frye, M., Harada, B.T., Behm, M., and He, C. (2018). RNA modifications in controlling gene expression during development. Science. 361, 1346-1349
  • Flores, J.V., Cordero-Espinoza, L., Oeztuerk-Winder, F., Andersson-Rolf, A., Selmi, T., Blanco, S., Tailor, J., Dietmann, S., and Frye, M. (2017). Cytosine-5 RNA methylation regulates neural stem cell differentiation and motility. Stem Cell Reports. 8, 112-124.
  • Blanco, S., Bandiera, R., Popis, M., Hussain, S., Lombard, P., Aleksic, J., Sajini, A., Tanna, H., Cortés-Garrido, R., Gkatza, N., Dietmann, S., and Frye, M. (2016). Stem cell function and stress response are controlled by protein synthesis. Nature. 534, 335–340.
  • Van Haute, L., Dietmann, S., Kremer, L., Hussain, S., Pearce,S.F., Powell, C.A., Rorbach, J., Lantaff, R., Blanco, S., Sauer, S., Kotzaeridou, U., Hoffmann, G.F., Memari, Y., Kolb-Kokocinski, A., Durbin, R., Frye, M.*, Prokisch, H.*, and Minczuk, M.* (2016). Deficient methylation and formylation of mt-tRNAMet wobble cytosine in a patient carrying mutations in NSUN3. Nature Comm. 30, 12039
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