Salerno-Kochan, A., Horn, A., Ghosh, P., Nithin, C., Kościelniak, A., Meindl, A., Strauss, D., Krutyhołowa, R., Rossbach, O., Bujnicki, J.M., Gaik, M., Medenbach, J., Glatt, S. (2022). Molecular insights into RNA recognition and gene regulation by the TRIM-NHL protein Mei-P26.  Life Sci Alliance 5(8): e202201418.

FBrf0253370

Research paper

The TRIM-NHL protein Meiotic P26 (Mei-P26) acts as a regulator of cell fate in Drosophila Its activity is critical for ovarian germline stem cell maintenance, differentiation of oocytes, and spermatogenesis. Mei-P26 functions as a post-transcriptional regulator of gene expression; however, the molecular details of how its NHL domain selectively recognizes and regulates its mRNA targets have remained elusive. Here, we present the crystal structure of the Mei-P26 NHL domain at 1.6 Å resolution and identify key amino acids that confer substrate specificity and distinguish Mei-P26 from closely related TRIM-NHL proteins. Furthermore, we identify mRNA targets of Mei-P26 in cultured Drosophila cells and show that Mei-P26 can act as either a repressor or activator of gene expression on different RNA targets. Our work reveals the molecular basis of RNA recognition by Mei-P26 and the fundamental functional differences between otherwise very similar TRIM-NHL proteins.

PMC9070667 (PMC) (EuropePMC)