title: A negative feedback mechanism revealed by functional analysis of the alternative isoforms of the Drosophila splicing regulator transformer-2.
abstract: The Drosophila sex determination gene transformer-2 (tra-2) is a splicing regulator that affects the sex-specific processing of several distinct pre-mRNAs. While the tra-2 gene itself is known to produce alternative mRNAs that together encode three different TRA-2 protein isoforms, the respective roles of these isoforms in affecting individual pre-mRNA targets has remained unclear. We have generated transgenic fly strains with mutations affecting specific TRA-2 isoforms to investigate their individual roles in regulating the alternative processing of doublesex, exuperantia and tra-2 pre-mRNA. Our results indicate that in somatic tissues two different isoforms function redundantly to direct female differentiation and female-specific doublesex pre-mRNA splicing. In the male germline, where tra-2 has an essential role in spermatogenesis, a single isoform was found to uniquely perform all necessary functions. This isoform appears to regulate its own synthesis during spermatogenesis through a negative feedback mechanism involving intron retention.
authors.affiliation: Department of Molecular Genetics, University of Texas, M. D. Anderson Cancer Center, Houston 77030, USA.
authors.forename: W
authors.initials: W
authors.lastname: Mattox
authors.forename: M E
authors.initials: ME
authors.lastname: McGuffin
authors.forename: B S
authors.initials: BS
authors.lastname: Baker
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D030801:Animals, Genetically Modified; D015342:DNA Probes; D004330:Drosophila / Q000235:genetics* / Q000502:physiology; D029721:Drosophila Proteins; D005246:Feedback; D005260:Female; D005298:Fertility; D017344:Genes, Insect; D008297:Male; D008969:Molecular Sequence Data; D012322:RNA Precursors / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012261:Ribonucleoproteins / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D012732:Sex Determination Analysis; D012733:Sex Differentiation; D013091:Spermatogenesis
chemical_list: D015342:DNA Probes; D029721:Drosophila Proteins; D012322:RNA Precursors; D012333:RNA, Messenger; D012261:Ribonucleoproteins; C066174:tra2 protein, Drosophila