Genomic organization, complex splicing pattern and expression of a human septin gene on chromosome 17q25.3
Genomic organization, complex splicing pattern and expression of a human septin gene on chromosome 17q25.3
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DOI：
10.1038/sj.onc.1204752
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发表时间：
2001-09-13
期刊：
影响因子：
8
通讯作者：
Russell, SEH
中科院分区：
文献类型：
--
作者：
McIlhatton, MA;Burrows, JF;Russell, SEH
Ov/BR Septin基因也是急性髓系白血病中MLL的融合伙伴，是参与胞质分裂和胞吐作用的新型GTP结合蛋白家族的成员。在这项研究中，我们描述了该基因的基因组和转录组织，详细描述了分布在240kb序列上的17个外显子。广泛的数据库分析确定了与Ov/BR Septin基因的新的、未识别的5‘剪接变体相对应的直系啮齿动物cDNA，使此类变体的总数增加到6个。我们报告说，发生在3‘端外显子体内非规范位点的剪接事件，通过非编码序列的1801或1849去除，并促进了在3’UTR端附近维持的44个氨基酸的二级开放阅读框架的访问。这些事件构成了一种新的编码安排，并代表了由真核基因实现的这种设计的第一个报告。不同的Ov/BR蛋白要么在氨基和羧基末端差别很小，要么等同于较大异构体的截短版本。用Ov/BR Septin 3‘UTR探针进行Northern分析，发现了4.4、4和3kb的三个转录本，后者仅限于所测试的组织的一个子集。对鉴定的Ov/BR Septin亚型的RT-PCR研究证实了一种复杂的转录模式，其中几种亚型显示出组织特异性的分布。到目前为止，还没有其他人类分隔素表现出这样的转录复杂性。
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 noncanonical 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 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.