Molecular insights into RNA recognition and gene regulation by the TRIM-NHL protein Mei-P26

• Main Authors: Bujnicki, J.M (Author), Gaik, M. (Author), Ghosh, P. (Author), Glatt, S. (Author), Horn, A. (Author), Kościelniak, A. (Author), Krutyhołowa, R. (Author), Medenbach, J. (Author), Meindl, A. (Author), Nithin, C. (Author), Rossbach, O. (Author), Salerno-Kochan, A. (Author), Strauss, D. (Author)
• Format: Article
• Language: English
• Published: NLM (Medline) 2022
• Online Access: View Fulltext in Publisher
• ISBN: 25751077 (ISSN)
• DOI: 10.26508/lsa.202201418

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. © 2022 Salerno-Kochan et al.