4 Nov

New publication from the lab

Good news: A manuscript from the lab has just been accepted for publication in the RNA Journal!

We have identified the protein Sister-of-Sex-Lethal (Ssx) as a novel repressor of translation. Ssx is a paralog of the master regulator of female development in Drosophila, Sex-lethal (Sxl), that acts as a repressor of male-specific lethal-2 (msl-2) mRNA translation. It employs two distinct and mutually reinforcing blocks to translation that operate on the 5’ and 3’ untranslated regions (UTRs) of msl-2 mRNA, respectively. While 5’ UTR-mediated translational control involves an upstream open reading frame, 3’ UTR-mediated regulation strictly requires the co-repressor protein Upstream of N-ras (Unr) which is recruited to the transcript by Sxl.

Ssx and Sxl have a comparable RNA-binding specificity and both proteins can associate with Uracil-rich RNA regulatory elements present in msl-2 mRNA. Moreover, both repress translation when bound to the 5’ UTR of msl-2. However, Ssx is inactive in 3’ UTR-mediated regulation as it cannot engage the co-repressor protein Unr. The difference in activity maps to the first RNA-recognition motif (RRM) of Ssx. Conversion of three amino acids within this domain into their Sxl counterpart results in a gain-of-function and repression via the 3’ UTR, allowing detailed insights into the evolutionary origin of the two proteins and into the molecular requirements of an important translation regulatory pathway.

Find the full text here.  RNA. 2017 Oct 31. pii: rna.063776.117. doi: 10.1261/rna.063776.117. [Epub ahead of print], PMID: 29089381

 

Leave a Reply

Your email address will not be published. Required fields are marked *