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| Subject Categories: Proteins |
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| The EMBO Journal
(2003) 22, 5571–5581, doi:10.1093/emboj/cdg539 |
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| A co-repressor assembly nucleated by Sex-lethal in the 3'UTR mediates translational control of Drosophila msl-2 mRNA |
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| Marica Grskovic1, Matthias W. Hentze1 and Fátima Gebauer2 |
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1 Gene Expression Programme, European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany 2 Present address: Centre de Regulació Genómica, Passeig Maritim 37–49, Planta 1, 08003 Barcelona, Spain To whom correspondence should be addressed Matthias W. Hentze, hentze@embl.de Received 5 June 2003; Revised 27 August 2003; Accepted 28 August 2003. |
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| Abstract |
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| Drosophila Sex-lethal (dSXL)-mediated translational repression of male-specific lethal 2 (msl-2) mRNA is essential for X-chromosome dosage compensation. Binding of dSXL to specific sites in both untranslated regions of msl-2 mRNA is necessary for inhibition of translation initiation. We describe the organization of dSXL as a translational regulator and show that the RNA binding and translational repressor functions are contained within the two RRM domains and a C-terminal heptapeptide extension. The repressor function is dormant unless dSXL binds to msl-2 mRNA with its own RRMs, because dSXL tethering via a heterologous RNA-binding peptide does not elicit translational inhibition. We reveal proteins that crosslink to the msl-2 3' untranslated region (3'UTR) and co-immunoprecipitate with dSXL in a fashion that requires its intact repressor domain and correlates with translational regulation. Translation competition and UV-crosslink experiments show that the 3'UTR msl-2 sequences adjacent to dSXL-binding sites are necessary to recruit titratable co-repressors. Our data support a model where dSXL binding to the 3'UTR of msl-2 mRNA activates the translational repressor domain, thereby enabling it to recruit co-repressors in a specific fashion. |
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| Keywords: dosage compensation, in vitro translation, post-transcriptional control, RNA–protein interactions, RNPs |
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