PT  - JOURNAL ARTICLE
AU  - Anna Salerno-Kochan
AU  - Andreas Horn
AU  - Pritha Ghosh
AU  - Chandran Nithin
AU  - Anna Kościelniak
AU  - Daniela Strauss
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  - 10.1101/2021.09.20.461029
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.09.20.461029
4099  - http://biorxiv.org/content/early/2021/09/21/2021.09.20.461029.short
4100  - http://biorxiv.org/content/early/2021/09/21/2021.09.20.461029.full
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.