The Tgif2 gene contains a retained intron within the coding sequence
The Tgif2 gene contains a retained intron within the coding sequence
复制标题
DOI：
10.1186/1471-2199-7-2
复制
发表时间：
2006-01-25
影响因子：
--
通讯作者：
Wotton, D
中科院分区：
文献类型：
--
作者：
Melhuish, TA;Wotton, D
背景：TGIF和TGIF2是同源结构域蛋白，它们作为转化生长因子β特异性的Smad转录共抑制因子。TGIF招募了包括mSin3和CtBP在内的一般抑制因子。相关的TGIF2蛋白具有类似的功能，但不与CtBP结合。除了抑制转化生长因子β激活的基因表达外，TGIF和TGIF2还通过直接与DNA结合来抑制基因表达。TGIF和TGIF2有两个主要的相似性块，包括同源结构域和保守的羧基末端抑制结构域。在这里，我们鉴定了小鼠Tgif2基因的两种剪接变体，并证明了Tgif2基因含有保留的内含子。结果：从小鼠的cDNA中，我们鉴定了两种不同剪接形式的Tgif2基因。一个剪接变体编码全长237个氨基酸的Tgif2，而较短的剪接变体导致从编码区中心移除39个密码子。这种选择性剪接形式的产生发生在老鼠的RNA中，但不发生在人类身上，而且这两种剪接形式在所有被分析的小鼠组织中都存在。人和小鼠的Tgif2编码序列包含一个保留的内含子，根据RT-PCR的评估，在小鼠的Tgif2中，通过剪接从大约25%-50%的RNA中去除了该内含子。这种剪接事件依赖于鼠标Tgif2编码序列中的序列。两种剪接形式的小鼠Tgif2编码的蛋白质都是活跃的转录抑制因子，并能抑制转化生长因子β依赖和非依赖转录。此外，我们还发现人和小鼠Tgif2与转录辅阻遏子mSin3相互作用。结论：这些数据表明Tgif2基因在第二个编码外显子内含有一个保留的内含子。这种保留的内含子不是在可检测的水平上从人类mRNA中移除的，而是在相当大比例的小鼠RNA中被拼接出来的。这种选择性剪接完全依赖于小鼠Tgif2编码序列中的序列，这表明存在外显子剪接增强子。小鼠Tgif2的两种剪接形式都能产生功能转录抑制蛋白。
Background: TGIF and TGIF2 are homeodomain proteins, which act as TGF beta specific Smad transcriptional corepressors. TGIF recruits general repressors including mSin3 and CtBP. The related TGIF2 protein functions in a similar manner, but does not bind CtBP. In addition to repressing TGF beta activated gene expression, TGIF and TGIF2 repress gene expression by binding directly to DNA. TGIF and TGIF2 share two major blocks of similarity, encompassing the homeodomain, and a conserved carboxyl terminal repression domain. Here we characterize two splice variants of the Tgif2 gene from mouse and demonstrate that the Tgif2 gene contains a retained intron.Results: By PCR from mouse cDNA, we identified two alternate splice forms of the Tgif2 gene. One splice variant encodes the full length 237 amino acid Tgif2, whereas the shorter form results in the removal of 39 codons from the centre of the coding region. The generation of this alternate splice form occurs with the mouse RNA, but not the human, and both splice forms are present in all mouse tissues analyzed. Human and mouse Tgif2 coding sequences contain a retained intron, which in mouse Tgif2 is removed by splicing from around 25 - 50% of RNAs, as assessed by RT-PCR. This splicing event is dependent on sequences within the mouse Tgif2 coding sequence. Both splice forms of mouse Tgif2 encode proteins which are active transcriptional repressors, and can repress both TGF beta dependent and independent transcription. In addition, we show that human and mouse Tgif2 interact with the transcriptional corepressor mSin3.Conclusion: These data demonstrate that the Tgif2 gene contains a retained intron, within the second coding exon. This retained intron is not removed from the human mRNA at a detectable level, but is spliced out in a significant proportion of mouse RNAs. This alternate splicing is dependent entirely on sequences within the mouse Tgif2 coding sequence, suggesting the presence of an exonic splicing enhancer. Both splice forms of mouse Tgif2 produce proteins which are functional transcriptional repressors.