Sex-lethal imparts a sex-specific function to UNR by recruiting it to the msl-2 mRNA 3′ UTR: translational repression for dosage compensation
Abstract
MSL-2 (male-specific lethal 2) is the limiting component of the Drosophila dosage compensation complex (DCC) that specifically increases transcription from the male X chromosome. Ectopic expression of MSL-2 protein in females causes DCC assembly on both X chromosomes and lethality. Inhibition of MSL-2 synthesis requires the female-specific protein sex-lethal (SXL), which binds to the msl-2 mRNA 5′ and 3′ untranslated regions (UTRs) and blocks translation through distinct UTR-specific mechanisms. Here, we purify translationally silenced msl-2 mRNPs and identify UNR (upstream of N-ras) as a protein recruited to the 3′ UTR by SXL. We demonstrate that SXL requires UNR as a corepressor for 3′-UTR-mediated regulation, imparting a female-specific function to the ubiquitously expressed UNR protein. Our results reveal a novel functional role for UNR as a translational repressor and indicate that UNR is a key component of a “fail-safe” dosage compensation regulatory system that prevents toxic MSL-2 synthesis in female cells.
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Footnotes
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Supplemental material is available at http://www.genesdev.org.
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Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.371406.
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↵3 Present address: Program in Developmental and Stem Cell Biology, University of California, San Francisco, CA 94143, USA.
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↵4 Corresponding author.
↵4 E-MAIL hentze{at}embl.de; FAX 49-6221-387518.
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- Accepted December 1, 2005.
- Received October 27, 2005.
- Cold Spring Harbor Laboratory Press