Alternative splicing generates a short BCL6 (BCL6S) isoform encoding a compact repressor.
Alternative splicing generates a short BCL6 (BCL6S) isoform encoding a compact repressor.
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DOI：
10.1016/j.bbrc.2008.07.116
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发表时间：
2008-10-17
影响因子：
3.1
通讯作者：
Chan, Wing C.
中科院分区：
文献类型：
--
作者：
Shen, Yulei;Ge, Baosheng;Ramachandrareddy, Himabindu;McKeithan, Timothy;Chan, Wing C.
BCL 6基因转录两种主要的mRNA亚型，变体1和变体2，它们具有不同的转录起始位点。然而，这两种亚型编码相同的BCL 6蛋白。最近，第三种变体从人海马cDNA文库（DB 465062）测序。在这项研究中，我们克隆并测序了一种新的BCL 6剪接异构体（BCL 6S），它缺乏编码BCL 6前两个锌指的外显子7。我们发现了一个剪接异构体，BCL 6S，不包括外显子7，但保留了BCL 6基因的六个锌指（ZFs）编码区的最后四个。BCL 6S mRNA和蛋白在表达BCL 6的人细胞系和组织中表达，但占BCL 6转录物或蛋白的一小部分。BCL 6阳性细胞中也可检测到BCL 6S蛋白。BCL-6S与BCL-6形成同源二聚体或异源二聚体，并与经典的BCL-6结合位点结合。荧光素酶报告基因分析表明，BCL 6S能有效抑制典型的BCL 6靶基因。BCL 6S是一个紧密的阻遏物，可能在正常和肿瘤性生殖中心B细胞中具有功能性作用。
BCL6 gene transcribes two main mRNA isoforms, variant 1 and variant 2, which have distinct transcription start sites. However, these two isoforms encode identical BCL6 protein. Recently, a third variant was sequenced from a human hippocampus cDNA library (DB465062). In this study, we cloned and sequenced a novel BCL6 spliced isoform (BCL6S) which lacks exon 7 that encodes the first two zinc fingers of BCL6. We found a splicing isoform, BCL6S, that excludes exon 7 but retains the last four of the six zinc fingers (ZFs) coding region of the BCL6 gene. BCL6S mRNA and protein were expressed in human cell lines and tissues that expressed BCL6, but accounted for a minor portion of BCL6 transcripts or protein. BCL6S protein was also detectable in BCL6 positive cells. BCL6S could form homodimers or heterodimers with BCL6 and could bind to classical BCL6 binding sites. Luciferase reporter assays demonstrated that BCL6S could effectively repress typical BCL6 target genes. BCL6S is a compact repressor that may have a functional role in normal and neoplastic germinal center B cells.
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