title: Alternative splicing of Pax3 produces a transcriptionally inactive protein.
abstract: Pax3, a member of the paired-class homeodomain family of transcription factors, plays an important role in embryonic development of neurepithelium and mesenchyme-derived tissues in the mouse and is an early marker for myogenic differentiation. In the present work we identify an alternative splicing event for endogenous Pax3 in primary mouse myoblasts. The resulting splice variant arises through the utilization of a previously unreported splice donor consensus sequence present at the junction between exons 7 and 8 in the Pax3 sequence. The use of this splice donor site in conjunction with the splice acceptor site present between intron 8 and exon 9 results in the deletion of exon 8 and removes a majority of the Pax3 transcriptional activation domain. Consistent with this fact, we demonstrate that the alternatively spliced form of Pax3 is transcriptionally inactive and that the presence of this isoform can effectively inhibit the activity of the full-length protein.
authors.affiliation: Department of Genetics, St. Jude Children's Research Hospital, 332 North Lauderdale, Memphis, TN 38105, USA.
authors.forename: Colin
authors.initials: C
authors.lastname: Pritchard
authors.forename: Gerard
authors.initials: G
authors.lastname: Grosveld
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Hollenbach
mesh_terms: D016475:3T3 Cells; D017398:Alternative Splicing / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D018076:DNA, Complementary / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005091:Exons / Q000235:genetics; D006801:Humans; D007438:Introns / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D017384:Sequence Deletion; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics*; D014162:Transfection
chemical_list: D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D000072041:PAX3 Transcription Factor; C489409:PAX3 protein, human; D051761:Paired Box Transcription Factors; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; C068686:Pax3 protein, mouse; D015500:Chloramphenicol O-Acetyltransferase