Our study of the activity of tha TRIM-NHL protein Mei-P26, a regulator of cell fate in Drosophila, has now been published at Life Science Alliance (doi 10.26508/lsa.202201418).

In a close collaboration with the labs of Sebastian Glatt (Max Planck Research Group at the Malopolska Centre of Biotechnology, Jagiellonian University Krakow, Poland) and Janusz Bujnicki (Laboratory of Bioinformatics and Protein Engineering, International Institute of Molecular and Cell Biology in Warsaw, Poland), we could solve the first high resolution structure of the Mei-P26 NHL domain and define a consensus RNA motif that it recognizes. Molecular dynamics simulations allowed us to predict and subsequently experimentally validate key amino acid residues involved specific RNA recognition, highlighting differences to other NHL domains. Using individual nucleotide resolution cross-linking and immunoprecipitation (iCLIP), we could identify RNA targets of Mei-P26 in cultured Drosophila cells and demonstrate the protein can either repress or activate its genuine mRNA targets. Regulation requires the NHL domain of the protein but is independent of its function as a ubiquitin ligase.

In particular, the last finding significantly expands our understanding of TRIM-NHL protein-mediated gene regulation. These proteins were previously considered to exclusively act as repressors of gene expression. Strikingly, Mei-P26 itself appears to lack any regulatory activity suggesting that the regulatory outcome is determined by the recruitment of different co-factors, some of which have previously been identified.