PT - JOURNAL ARTICLE AU - Anna Salerno-Kochan AU - Andreas Horn AU - Pritha Ghosh AU - Chandran Nithin AU - Anna Kościelniak AU - Andreas Meindl AU - Daniela Strauss AU - Rościsław Krutyhołowa AU - Oliver Rossbach AU - Janusz M Bujnicki AU - Monika Gaik AU - Jan Medenbach AU - Sebastian Glatt TI - Molecular insights into RNA recognition and gene regulation by the TRIM-NHL protein Mei-P26 AID - 10.26508/lsa.202201418 DP - 2022 Aug 01 TA - Life Science Alliance PG - e202201418 VI - 5 IP - 8 4099 - https://www.life-science-alliance.org/content/5/8/e202201418.short 4100 - https://www.life-science-alliance.org/content/5/8/e202201418.full SO - Life Sci. Alliance2022 Aug 01; 5 AB - 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.