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A co‐repressor assembly nucleated by Sex‐lethal in the 3′UTR mediates translational control of Drosophila msl‐2 mRNA
Author(s) -
Grskovic Marica,
Hentze Matthias W.,
Gebauer Fátima
Publication year - 2003
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/cdg539
Subject(s) - biology , repressor , messenger rna , genetics , untranslated region , three prime untranslated region , translation (biology) , drosophila (subgenus) , microbiology and biotechnology , translational regulation , gene , gene expression
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.