title: Genomic organization, complex splicing pattern and expression of a human septin gene on chromosome 17q25.3.
abstract: The Ov/Br septin gene, which is also a fusion partner of MLL in acute myeloid leukaemia, is a member of a family of novel GTP binding proteins that have been implicated in cytokinesis and exocytosis. In this study, we describe the genomic and transcriptional organization of this gene, detailing seventeen exons distributed over 240 kb of sequence. Extensive database analyses identified orthologous rodent cDNAs that corresponded to new, unidentified 5' splice variants of the Ov/Br septin gene, increasing the total number of such variants to six. We report that splicing events, occurring at non-canonical sites within the body of the 3' terminal exon, remove either 1801 bp or 1849 bp of non-coding sequence and facilitate access to a secondary open reading frame of 44 amino acids maintained near the end of the 3' UTR. These events constitute a novel coding arrangement and represent the first report of such a design being implemented by a eukaryotic gene. The various Ov/Br proteins either differ minimally at their amino and carboxy termini or are equivalent to truncated versions of larger isoforms. Northern analysis with an Ov/Br septin 3' UTR probe reveals three transcripts of 4.4, 4 and 3 kb, the latter being restricted to a sub-set of the tissues tested. Investigation of the identified Ov/Br septin isoforms by RT-PCR confirms a complex transcriptional pattern, with several isoforms showing tissue-specific distribution. To date, none of the other human septins have demonstrated such transcriptional complexity.
authors.affiliation: Department of Oncology, The Cancer Centre, Queen's University Belfast, Belfast BT9 7AB, UK.
authors.forename: M A
authors.initials: MA
authors.lastname: McIlhatton
authors.forename: J F
authors.initials: JF
authors.lastname: Burrows
authors.forename: P G
authors.initials: PG
authors.lastname: Donaghy
authors.forename: S
authors.initials: S
authors.lastname: Chanduloy
authors.forename: P G
authors.initials: PG
authors.lastname: Johnston
authors.forename: S E
authors.initials: SE
authors.lastname: Russell
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D001483:Base Sequence; D002874:Chromosome Mapping; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D003598:Cytoskeletal Proteins / Q000737:chemistry / Q000235:genetics*; D019204:GTP-Binding Proteins / Q000737:chemistry / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D015894:Genome, Human; D006801:Humans; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics*; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D003598:Cytoskeletal Proteins; D009363:Neoplasm Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; D019204:GTP-Binding Proteins