Salerno-Kochan, A.; Horn, A.; Ghosh, P.; Nithin, C.; Koscielniak, A.; Meindl, A.; Strauss, D.; Krutyholowa, R.; Rossbach, O.; Bujnicki, J.M.; Gaik, M.; Medenbach, J.; Glatt, S.: Molecular insights into RNA recognition and gene regulation by the TRIM-NHL protein Mei-P26. Langmuir 5 (2022), p. e202201418/1-17
10.26508/lsa.202201418
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Abstract:
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.