@article {49686,
	title = {Sex-lethal splicing autoregulation in vivo: interactions between SEX-LETHAL, the U1 snRNP and U2AF underlie male exon skipping.},
	journal = {Development},
	volume = {130},
	year = {2003},
	month = {2003 Feb},
	pages = {463-71},
	abstract = {<p>Alternative splicing of the Sex-lethal pre-mRNA has long served as a model example of a regulated splicing event, yet the mechanism by which the female-specific SEX-LETHAL RNA-binding protein prevents inclusion of the translation-terminating male exon is not understood. Thus far, the only general splicing factor for which there is in vivo evidence for a regulatory role in the pathway leading to male-exon skipping is sans-fille (snf), a protein component of the spliceosomal U1 and U2 snRNPs. Its role, however, has remained enigmatic because of questions about whether SNF acts as part of an intact snRNP or a free protein. We provide evidence that SEX-LETHAL interacts with SANS-FILLE in the context of the U1 snRNP, through the characterization of a point mutation that interferes with both assembly into the U1 snRNP and complex formation with SEX-LETHAL. Moreover, we find that SEX-LETHAL associates with other integral U1 snRNP components, and we provide genetic evidence to support the biological relevance of these physical interactions. Similar genetic and biochemical approaches also link SEX-LETHAL with the heterodimeric splicing factor, U2AF. These studies point specifically to a mechanism by which SEX-LETHAL represses splicing by interacting with these key splicing factors at both ends of the regulated male exon. Moreover, because U2AF and the U1 snRNP are only associated transiently with the pre-mRNA during the course of spliceosome assembly, our studies are difficult to reconcile with the current model that proposes that the SEX-LETHAL blocks splicing at the second catalytic step, and instead argue that the SEX-LETHAL protein acts after splice site recognition, but before catalysis begins.</p>},
	keywords = {Alternative Splicing, Amino Acid Sequence, Animals, Animals, Genetically Modified, Drosophila melanogaster, Drosophila Proteins, Exons, Female, Gene Expression Regulation, Developmental, Genes, Insect, Homeostasis, Male, Models, Genetic, Molecular Sequence Data, Nuclear Proteins, Point Mutation, Ribonucleoprotein, U1 Small Nuclear, Ribonucleoproteins, RNA Splicing, RNA-Binding Proteins, Sequence Homology, Amino Acid, Sex Differentiation},
	issn = {0950-1991},
	author = {Nagengast, Alexis A and Stitzinger, Shane M and Tseng, Chin-Hsiu and Mount, Stephen M and Salz, Helen K}
}
@article {49696,
	title = {Genetic enhancement of RNA-processing defects by a dominant mutation in B52, the Drosophila gene for an SR protein splicing factor.},
	journal = {Mol Cell Biol},
	volume = {15},
	year = {1995},
	month = {1995 Nov},
	pages = {6273-82},
	abstract = {<p>SR proteins are essential for pre-mRNA splicing in vitro, act early in the splicing pathway, and can influence alternative splice site choice. Here we describe the isolation of both dominant and loss-of-function alleles of B52, the gene for a Drosophila SR protein. The allele B52ED was identified as a dominant second-site enhancer of white-apricot (wa), a retrotransposon insertion in the second intron of the eye pigmentation gene white with a complex RNA-processing defect. B52ED also exaggerates the mutant phenotype of a distinct white allele carrying a 5{\textquoteright} splice site mutation (wDR18), and alters the pattern of sex-specific splicing at doublesex under sensitized conditions, so that the male-specific splice is favored. In addition to being a dominant enhancer of these RNA-processing defects, B52ED is a recessive lethal allele that fails to complement other lethal alleles of B52. Comparison of B52ED with the B52+ allele from which it was derived revealed a single change in a conserved amino acid in the beta 4 strand of the first RNA-binding domain of B52, which suggests that altered RNA binding is responsible for the dominant phenotype. Reversion of the B52ED dominant allele with X rays led to the isolation of a B52 null allele. Together, these results indicate a critical role for the SR protein B52 in pre-mRNA splicing in vivo.</p>},
	keywords = {Alleles, Amino Acid Sequence, Animals, Base Sequence, DNA Primers, Drosophila melanogaster, Drosophila Proteins, Frameshift Mutation, Genes, Dominant, Genes, Insect, Molecular Sequence Data, Nuclear Proteins, Phosphoproteins, Point Mutation, Protein Structure, Tertiary, Proteins, RNA Splicing, RNA-Binding Proteins, Sequence Deletion, Sex Determination Analysis},
	issn = {0270-7306},
	author = {Peng, X and Mount, S M}
}
