Distinct regulatory programs establish widespread sex-specific alternative splicing in Drosophila melanogaster
13.01.2011
Hartmann B, Castelo R, Miñana B, Peden E, Blanchette M, Rio DC, Singh R, Valcárcel J.
RNA 17(3): 453-68
Sex-lethal, a female-specific RNA binding protein, controls sex determination in Drosophila melanogaster by regulating a cascade of alternative splicing events culminating in expression of distinct sex-specific transcription factor isoforms. Using genome-wide splicing-sensitive microarrays, we find evidence for sex-specific alternative splicing affecting more than 500 genes, suggesting an extensive contribution of differential RNA processing to sex determination. Our results also indicate that regulation of a significant fraction of the novel sex-specific alternative splicing differences is not under the direct control of the Sex-lethal cascade and is tissue-restricted, implying regulatory programs distinct from the classical pathway. We also find extensive sex-specific differences in expression and alternative splicing of genes encoding RNA binding proteins, and report results supporting that some of these differences contribute to sex-specific splicing. Our most intriguing finding is that depletion of the germline in flies, using the maternal effect tudor mutant, affects sex-specific splicing of genes expressed in distant tissues, suggesting either novel functions for products of the tudor gene locus or a role for germline signals in splicing regulation.