RT Journal Article
SR Electronic
T1 Molecular insights into RNA recognition and gene regulation by the TRIM-NHL protein Mei-P26
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202201418
DO 10.26508/lsa.202201418
VO 5
IS 8
A1 Anna Salerno-Kochan
A1 Andreas Horn
A1 Pritha Ghosh
A1 Chandran Nithin
A1 Anna Kościelniak
A1 Andreas Meindl
A1 Daniela Strauss
A1 Rościsław Krutyhołowa
A1 Oliver Rossbach
A1 Janusz M Bujnicki
A1 Monika Gaik
A1 Jan Medenbach
A1 Sebastian Glatt
YR 2022
UL https://www.life-science-alliance.org/content/5/8/e202201418.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.