Identification, basic characterization and evolutionary analysis of differentially spliced mRNA isoforms of human YAP1 gene.
Identification, basic characterization and evolutionary analysis of differentially spliced mRNA isoforms of human YAP1 gene.
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DOI：
10.1016/j.gene.2012.08.025
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发表时间：
2012-11-10
期刊：
影响因子：
3.5
通讯作者：
Sudol M
中科院分区：
文献类型：
--
作者：
Gaffney CJ;Oka T;Mazack V;Hilman D;Gat U;Muramatsu T;Inazawa J;Golden A;Carey DJ;Farooq A;Tromp G;Sudol M
YAP1基因编码一种强大的新癌基因和干细胞因子。然而，在一些癌症中，YAP1基因起到了肿瘤抑制的作用。目前，该基因及其产物得到了广泛的研究，并在细胞和动物模型中用作转基因。在这里，我们报告了YAP1基因的4个新的潜在的基因剪接异构体，使总的异构体数量达到8个。我们在一组人体组织中检测了所有8个YAP1异构体，并用实时荧光定量聚合酶链式反应检测了YAP1最长的异构体(YAP1-2δ)的表达。所有YAP1亚型在人类白细胞中几乎检测不到，而在其他人类组织中则有较高水平的表达。我们分析了在不同后生动物中产生选择性剪接YAP1转录本的基因组区域的结构。我们发现利用外显子6的YAP1亚型是随着羊膜的出现而进化而来的。有趣的是，与在两个YAP1(α)亚型中发现的完整的亮氨酸拉链相比，包含外显子5延伸、外显子6或两者兼有的6个YAP1亚型在预测的蛋白质产品中的亮氨酸拉链区域将被破坏。这一观察结果对YAP1信号有直接的功能影响。我们还提出了YAP1基因mRNA剪接变异体的标准化命名，这将有助于表征YAP1基因潜在蛋白产物之间的信号差异。
The YAP1 gene encodes a potent new oncogene and stem cell factor. However, in some cancers, the YAP1 gene plays a role of tumor suppressor. At present, the gene and its products are intensely studied and its cDNAs are used as transgenes in cellular and animal models. Here, we report 4 new potential mRNA splicing isoforms of the YAP1 gene, bringing the total number of isoforms to 8. We detected all 8 YAP1 isoforms in a panel of human tissues and evaluated the expression of the longest isoform of YAP1 (YAP1-2δ) using Real Time PCR. All YAP1 isoforms are barely detectable in human leukocytes compared to fair levels of expression found in other human tissues. We analyzed the structure of the genomic region that gave rise to alternatively spliced YAP1 transcripts in different metazoans. We found that YAP1 isoforms, which utilize exon 6 emerged in evolution with the appearance of amniotes. Interestingly, 6 YAP1 isoforms, which contain the exon 5 extension, exon 6 or both would have their leucine zipper region disrupted in the predicted protein product, compared to the intact leucine zipper found in two YAP1 (α) isoforms. This observation has direct functional ramifications for YAP1 signaling. We also propose a normalized nomenclature for the mRNA splice variants of YAP1 gene, which should aid in the characterization of signaling differences among the potential protein products of the YAP1 gene.
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影响因子：
8
作者：
Oka, T.;Schmitt, A. P.;Sudol, M.
通讯作者：
Sudol, M.
影响因子：
4.8
作者：
SUDOL, M;BORK, P;LEHMAN, D
通讯作者：
LEHMAN, D
影响因子：
8
作者：
Sundvall, M.;Peri, L.;Elenius, K.
通讯作者：
Elenius, K.
影响因子：
64.5
作者：
OSHEA, EK;RUTKOWSKI, R;KIM, PS
通讯作者：
KIM, PS
DOI：
10.1084/jem.20111692
发表时间：
2012-04-09
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Mou F;Praskova M;Xia F;Van Buren D;Hock H;Avruch J;Zhou D
通讯作者：
Zhou D