biostudies-literatureSalerno-Kochan AIIMCB Statutory FundsGerman Research FoundationFoundation for Polish ScienceNational Science CentreGerman Federal Ministry of Education and ResearchEuropean Union’s Horizon 2020 research and innovation programmee202201418https://www.ebi.ac.uk/biostudies/studies/S-EPMC9070667biostudies-literatureUnknown5(8)The TRIM-NHL protein Meiotic P26 (Mei-P26) acts as a regulator of cell fate in <i>Drosophila</i> 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 <i>Drosophila</i> cells and show that Mei-P26 can act as either a repressor or activator of gene expression Life science allianceMolecular insights into RNA recognition and gene regulation by the TRIM-NHL protein Mei-P26.PMC9070667UMO-2015/19/P/NZ1/0251466577801ZX1401D2017/26/A/NZ1/01083TECH CORE FACILITY/2017-4/6SFB960 TP B11, ME4238/1-1UMO-2019/32/T/NZ1/00420TEAM/2016-3/18RTG2355 325443116Medenbach JKoscielniak AStrauss DBujnicki JMKrutyholowa RHorn ASalerno-Kochan ANithin CRossbach OGhosh PGaik MGlatt SMeindl AfalseMolecular insights into RNA recognition and gene regulation by the TRIM-NHL protein Mei-P26.The TRIM-NHL protein Meiotic P26 (Mei-P26) acts as a regulator of cell fate in <i>Drosophila</i> 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 <i>Drosophila</i> cells and show that Mei-P26 can act as either a repressor or activator of gene expression 2022-01-01T00:00:00Z2022 Aug2026-05-31T20:59:16.672Z2025-02-19T04:20:58.653ZS-EPMC90706673551283510.26508/lsa.202201418