RT Journal Article
SR Electronic
T1 Molecular insights into RNA recognition and gene regulation by the TRIM-NHL protein Mei-P26
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.09.20.461029
DO 10.1101/2021.09.20.461029
A1 Anna Salerno-Kochan
A1 Andreas Horn
A1 Pritha Ghosh
A1 Chandran Nithin
A1 Anna Kościelniak
A1 Daniela Strauss
A1 Oliver Rossbach
A1 Janusz M. Bujnicki
A1 Monika Gaik
A1 Jan Medenbach
A1 Sebastian Glatt
YR 2021
UL http://biorxiv.org/content/early/2021/09/21/2021.09.20.461029.abstract
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.