Functioning of the Drosophila integral U1/U2 protein Snf independent of U1and U2 small nuclear ribonucleoprotein particles is revealed by snf(+) gene dose effects

Snf, encoded by sans fills, is the Drosophila homolog of mammalian U1A and U2B " and is an integral component of U1 and U2 small nuclear ribonucleopro tein particles (snRNPs). Surprisingly, changes in the level of this houseke eping protein can specifically affect autoregulatory activity of the RNA-bi nding protein Sex-lethal (Sxl) in an action that we infer must be physicall y separate from Snf's functioning within snRNPs. Sri is a master switch gen e that controls its own pre-mRNA splicing as well as splicing for subordina te switch genes that regulate sex determination and dosage compensation. Ex ploiting an unusual new set of mutant Sri alleles in an in vivo assay, we s how that Snf is rate-limiting for Sri autoregulation when Sri levels are lo w. In such situations, increasing either maternal or zygotic snf(+) dose en hances the positive autoregulatory activity of Sri for Sri somatic pre-mRNA splicing without affecting Sri activities toward its other RNA targets. In contrast, increasing the dose of genes encoding either the integral U1 snR NP protein U1-70k. or the integral U2 snRNP protein SF3a(60), has no effect . Increased snf(+) enhances Sri autoregulation even when U1-70k and SF3a(60 ) are reduced by mutation to levels that, in the case of SF3a(60), demonstr ably interfere with Sri autoregulation. The observation that increased snf( +) does not suppress other phenotypes associated with mutations that reduce U1-70k or SF3a(60) is additional evidence that snf(+) dose effects are not caused by increased snRNP levels. Mammalian U1A protein, like Snf. has a s nRNP-independent function.