Functional domains of Drosophila UNR in translational control.

RNA
Irina Abaza, Fátima Gebauer

Abstract

Translational repression of male-specific-lethal 2 (msl-2) mRNA by Sex-lethal (SXL) is an essential regulatory step of X chromosome dosage compensation in Drosophila. Translation inhibition requires that SXL recruits the protein upstream of N-ras (UNR) to the 3' UTR of msl-2 mRNA. UNR is a conserved, ubiquitous protein that contains five cold-shock domains (CSDs). Here, we dissect the domains of UNR required for translational repression and complex formation with SXL and msl-2 mRNA. Using gel-mobility shift assays, the domain involved in interactions with SXL and msl-2 was mapped specifically to the first CSD (CSD1). Indeed, excess of a peptide containing this domain derepressed msl-2 translation in vitro. The CSD1 of human UNR can also form a complex with SXL and msl-2. Comparative analyses of the CSDs of the Drosophila and human proteins together with site-directed mutagenesis experiments revealed that three exposed residues within CSD1 are required for complex formation. Tethering assays showed that CSD1 is not sufficient for translational repression, indicating that UNR binding to SXL and msl-2 can be distinguished from translation inhibition. Repression by tethered UNR requires residues from both the amino-terminal Q-rich ...Continue Reading

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Citations

Oct 5, 2013·Human Gene Therapy Methods·Thomas H HutsonRafael J Yáñez-Muñoz
Nov 30, 2011·Epigenomics·Jeffrey E Squires, Thomas Preiss
Mar 31, 2011·Future Medicinal Chemistry·Tsuyoshi YamamotoSatoshi Obika
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Dec 1, 2012·Briefings in Functional Genomics·Emilia Szostak, Fátima Gebauer
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Mar 13, 2020·Life Science Alliance·Pavan Kumar KakumaniMartin J Simard
Jul 23, 2020·Cell Reports·Nele Merret HollmannJanosch Hennig
Apr 10, 2021·Oncogene·Pavan Kumar KakumaniMartin J Simard

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