Genomic organization, complex splicing pattern and expression of a human septin gene on chromosome 17q25.3

• Published in: Oncogene Vol. 20; no. 41; pp. 5930 - 5939
• Main Authors: MCILHATTON, Michael A, BURROWS, James F, DONAGHY, Paul G, CHANDULOY, Severine, JOHNSTON, Patrick G, RUSSELL, S. E
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing 13.09.2001; Nature Publishing Group
• Subjects: 3' Untranslated regions; Acute myeloid leukemia; Alternative Splicing; Amino Acid Sequence; Base Sequence; Biological and medical sciences; Cell division; Cell physiology; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Chromosome 17; Chromosome Mapping; Chromosomes; Chromosomes, Human, Pair 17 - genetics; Cytokinesis; Cytoskeletal Proteins - chemistry; Cytoskeletal Proteins - genetics; Exocytosis; Exons; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation, Neoplastic; Genes; Genome, Human; Genomics; GTP-Binding Proteins - chemistry; GTP-Binding Proteins - genetics; Humans; Insects; Isoforms; Leukemia; Molecular and cellular biology; Molecular Sequence Data; Neoplasm Proteins - genetics; Oncology; Ov/Br septin gene; Protein Isoforms - chemistry; Protein Isoforms - genetics; Proteins; RNA, Messenger - metabolism; Septin; Transcription; Human; Organization; Splicing; Gene expression; Genomics; Chromosome A
• DOI: 10.1038/sj.onc.1204752
• ISSN: 0950-9232

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.