Stem cell homeostasis and disease
Our lab focuses on the identification and characterization of post-transcriptional modifications that regulate the maintenance of adult stem cells. We further explore whether modulation of RNA-methylation pathways can help to protect from human diseases such as cancer.
RNA methylation and stem cell function
The decision of stem cells to self-renew, proliferate or undergo differentiation is initiated by external stimuli that are linked to intrinsic networks of transcriptional, post-transcriptional and translational processes. RNA plays versatile roles in the transcription and translation of genes into proteins. In contrast to the far-reaching cellular functions of RNA, its building blocks are simple and only consist of four different nucleobases. To expand the functional capacity of RNA molecules and increase its capacity to encode information, each nucleobase can be chemically modified. To date over 100 known chemical modifications are known in RNA and many of those are functionally indispensable for protein translation because they regulate messenger RNA stability, splicing and protein translation efficiency and accuracy.
One of the most common chemical RNA modification is methylation. Cytosine-5 methylation in RNA is mediated by 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 lab dissects the roles of RNA methyltransferases and their methylated target RNAs in normal development, human disease and cancer.
Our current research themes are:
- The dynamic deposition of 5-methylcytosine (m5C) into RNA
- The functional roles of m5C in RNA metabolism
- The importance of m5C methylases in development and diseases
Recent selected publications
- 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-tRNA(Met) wobble cytosine in a patient carrying mutations in NSUN3. Nat Commun. 30:12039.
- 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.
- Driskell I., Oeztuerk-Winder F., Humphreys P., and Frye M. (2015). Genetically induced cell death in bulge stem cells reveals their redundancy for hair and epidermal regeneration. Stem Cells. 33:988-98.
- Blanco S., Dietmann S., Flores J.V., Hussain S., Kutter C., Humphreys P., Lukk M., Lombard P., Treps L., Popis M., Kellner S., Hölter S.M., Garrett L., Wurst W., Becker L., Klopstock T., Fuchs H., Gailus-Durner V. , Hrabĕ de Angelis M., Káradóttir R.T., Helm M., Ule J., Gleeson J.G., Odom D.T., Frye.M. (2014). Aberrant methylation of tRNAs links cellular stress to neuro-developmental diseases. EMBO J. 33: 2020-39.
- Hussain S., Sajini A.A., Blanco S., Dietmann S., Lombard P., Sugimoto Y., Paramor M., Gleeson J.G., Odom D.T., Ule J. and Frye M. (2013). NSun2-mediated cytosine-5 methylation of Vault non-coding RNA determines its processing into regulatory small RNAs. Cell Reports. 4:255-61.
Page updated : 27 July 2016