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

The Ov/Br septin gene, which is also a fusion partner of MLL in acute myelo id leukaemia, is a member of a family of novel GTP binding proteins that ha ve been implicated in cytokinesis and exocytosis. In this study, we describ e the genomic and transcriptional organization of this gene, detailing seve nteen exons distributed over 240 kb of sequence. Extensive database analyse s identified orthologous rodent cDNAs that corresponded to new, unidentifie d 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 nonc anonical sites within the body of the 3 ' terminal exon, remove either 1801 by or 1849 by 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 firs t report of such a design being implemented by a eukaryotic gene. The vario us Ov/Br proteins either differ minimally at their amino and carboxy termin i or are equivalent to truncated versions of larger isoforms. Northern anal ysis 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-speci fic distribution. To date, none of the other human septins have demonstrate d such transcriptional complexity.