Gracjan Michlewski

Dr Michlewski graduated from the Adam Mickiewicz University. In 2005, he obtained PhD in Biochemistry with distinction at Polish Academy of Sciences, Institute of Bioorganic Chemistry, Poznan. In 2012, he was awarded habilitation degree by Polish

Academy of Sciences for his work on ‘Regulation of microRNA biogenesis. Between 2005 and 2010 he has been a post-doctoral researcher in the laboratory of Prof. Javier F. Caceres at the Medical Research Council, Human Genetics Unit, Edinburgh, UK. In 2010 he was awarded Medical Research Council Career Development Award and opened his laboratory at the Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh, UK. In 2018 he has been promoted to Senior Lecturer at the School of Biomedical Sciences, University of Edinburgh, UK. This post was linked to an Associate Professor teaching position at the Zhejiang University-University of Edinburgh, Haining, China. In 2020, Dr Michlewski has been promoted to Reader at the University of Edinburgh, Edinburgh, UK. 

In 2019 Dr Michlewski won a competition to open Dioscuri Centre for RNA-Protein Interactions in Human Health and Disease at the International Institute of Molecular and Cell Biology in Warsaw, funded by the Max Planck Society and National Science Centre in Poland. He initiated the Dioscuri Centre in 2021. He is also supported by the NAWA Polish Returns grant, which he obtained in 2020.

Dr Michlewski’s biggest discoveries include identification of conserved elements in the small non-coding microRNAs (miRNAs) precursors (1) and auxiliary cofactors that regulate biogenesis of neuronal and non-neuronal miRNAs (2-9). He provided the evidence that miRNA auxiliary cofactors can be targeted by natural compounds to reactivate production of neuronal miRNA-7, which is implicated in aetiology of Parkinson’s Disease (10). He has discovered that a key factor in the innate immune response to RNA viruses, including Influenza, Coronavirus or Ebola – E3 ubiquitin ligase TRIM25 – is a novel RNA-binding protein (5). He has uncovered TRIM25’s RNA-binding domain and showed that RNA-binding properties of TRIM25 are crucial for its E3 ubiquitin ligase activity (11). Finally, he developed an original technique based on the RNA pull-down combined with quantitative mass spectrometry (12). This technique has been successfully used to identify numerous physiologically relevant RNA-protein interactions (3-5,9,13).

  1. Michlewski, G., Guil, S., Semple, C.A. and Caceres, J.F. (2008) Posttranscriptional regulation of miRNAs harboring conserved terminal loops. Mol Cell, 32, 383-393.
  2. Michlewski, G. and Caceres, J.F. (2010) Antagonistic role of hnRNP A1 and KSRP in the regulation of let-7a biogenesis. Nat Struct Mol Biol, 17, 1011-1018.
  3. Choudhury, N.R., de Lima Alves, F., de Andres-Aguayo, L., Graf, T., Caceres, J.F., Rappsilber, J. and Michlewski, G. (2013) Tissue-specific control of brain-enriched miR-7 biogenesis. Genes Dev, 27, 24-38.
  4. Nowak, J.S., Choudhury, N.R., de Lima Alves, F., Rappsilber, J. and Michlewski, G. (2014) Lin28a regulates neuronal differentiation and controls miR-9 production. Nat Commun, 5, 3687.
  5. Choudhury, N.R., Nowak, J.S., Zuo, J., Rappsilber, J., Spoel, S.H. and Michlewski, G. (2014) Trim25 Is an RNA-Specific Activator of Lin28a/TuT4-Mediated Uridylation. Cell Rep, 9, 1265-1272.
  6. Nowak, J.S., Hobor, F., Downie Ruiz Velasco, A., Choudhury, N.R., Heikel, G., Kerr, A., Ramos, A. and Michlewski, G. (2017) Lin28a uses distinct mechanisms of binding to RNA and affects miRNA levels positively and negatively. RNA, 23, 317-332.
  7. Kooshapur, H., Choudhury, N.R., Simon, B., Muhlbauer, M., Jussupow, A., Fernandez, N., Jones, A.N., Dallmann, A., Gabel, F., Camilloni, C. et al. (2018) Structural basis for terminal loop recognition and stimulation of pri-miRNA-18a processing by hnRNP A1. Nat Commun, 9, 2479.
  8. Michlewski, G. and Caceres, J.F. (2019) Post-transcriptional control of miRNA biogenesis. RNA, 25, 1-16.
  9. Downie Ruiz Velasco, A., Welten, S.M.J., Goossens, E.A.C., Quax, P.H.A., Rappsilber, J., Michlewski, G. and Nossent, A.Y. (2019) Posttranscriptional Regulation of 14q32 MicroRNAs by the CIRBP and HADHB during Vascular Regeneration after Ischemia. Mol Ther Nucleic Acids, 14, 329-338.
  10. Kumar, S., Downie Ruiz Velasco, A. and Michlewski, G. (2017) Oleic Acid Induces MiR-7 Processing through Remodeling of Pri-MiR-7/Protein Complex. J Mol Biol, 429, 1638-1649.
  11. Choudhury, N.R., Heikel, G., Trubitsyna, M., Kubik, P., Nowak, J.S., Webb, S., Granneman, S., Spanos, C., Rappsilber, J., Castello, A. et al. (2017) RNA-binding activity of TRIM25 is mediated by its PRY/SPRY domain and is required for ubiquitination. BMC Biol, 15, 105.
  12. Choudhury, N.R. and Michlewski, G. (2019) Quantitative identification of proteins that influence miRNA biogenesis by RNA pull-down-SILAC mass spectrometry (RP-SMS). Methods, 152, 12-17.