F. Gebauer et al., THE DROSOPHILA SPLICING REGULATOR SEX-LETHAL DIRECTLY INHIBITS TRANSLATION OF MALE-SPECIFIC-LETHAL-2 MESSENGER-RNA, RNA, 4(2), 1998, pp. 142-150
Male-specific expression of the protein male-specific-lethal 2 (MSL-2)
controls dosage compensation in Drosophila. msl-2 gene expression is
inhibited in females by Sex-lethal (SXL), an RNA binding protein known
to regulate pre-mRNA splicing. An intron present at the 5' untranslat
ed region (UTR) of msl-2 mRNA contains putative SXL binding sites and
is retained in female flies, Here we show that SXL plays a dual role i
n the inhibition of msl-2 expression, Cotransfection of Drosophila Sch
neider cells with an SXL expression vector and a reporter containing t
he 5' UTR of msl-2 mRNA resulted in retention of the 5' UTR intron and
efficient accumulation of the unspliced mRNA in the cytoplasm, where
its translation was blocked by SXL, but not by the intron per se, Both
splicing and translation inhibition by SXL were recapitulated in vitr
o and found to be dependent upon SXL binding to high-affinity sites wi
thin the intron, showing that SXL directly regulates these events, Our
data reveal a coordinated mechanism for the regulation of msl-2 expre
ssion by the same regulatory factor: SXL enforces intron retention in
the nucleus and subsequent translation inhibition in the cytoplasm.