Identification, basic characterization and evolutionary analysis of differentially spliced mRNA isoforms of human YAP1 gene

被引：81

作者：

Gaffney, Christian J. ^{[1
]}

Oka, Tsutomu ^{[1
]}

Mazack, Virginia ^{[1
]}

Hilman, Dror ^{[2
]}

Gat, Uri ^{[2
]}

Muramatsu, Tomoki ^{[3
]}

Inazawa, Johji ^{[3
]}

Golden, Alicia ^{[4
]}

Carey, David J. ^{[4
]}

Farooq, Amjad ^{[5
,6
]}

Tromp, Gerard ^{[1
]}

Sudol, Marius ^{[1
,7
]}

机构：

[1] Weis Ctr Res, Geisinger Clin, Lab Signal Transduct & Prote Profiling, Danville, PA 17821 USA

[2] Hebrew Univ Jerusalem, Alexander Silberman Inst Life Sci, Dept Cell & Dev Biol, IL-91904 Jerusalem, Israel

[3] Tokyo Med & Dent Univ, Dept Mol Cytogenet, Bunkyo Ku, Tokyo 1138510, Japan

[4] Weis Ctr Res, Geisinger Clin, Lab Extracellular Matrix, Danville, PA 17821 USA

[5] Univ Miami, Leonard Miller Sch Med, Dept Biochem & Mol Biol, Miami, FL 33136 USA

[6] Univ Miami, Leonard Miller Sch Med, USylvester Braman Family Breast Canc Inst, Miami, FL 33136 USA

[7] Mt Sinai Sch Med, Dept Med, New York, NY 10029 USA

来源：

GENE | 2012年 / 509卷 / 02期

基金：

美国国家卫生研究院;

关键词：

Alternative splicing; WW domains; Leucine zipper; Quantitative RT-PCR; WW DOMAIN; LEUCINE ZIPPER; PROTEIN YAP; PATHWAY; ACTIVATION; ONCOGENE; ERBB4; BINDS; ACTS; MST2;

D O I：

10.1016/j.gene.2012.08.025

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

The YAP1 gene encodes a potent new oncogene and stein 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 (YAP1-2 delta) 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 (alpha) isoforms. This observation has direct functional ramifications for YAP1 signaling. We also propose a normalized nomenclature for the mRNA splice variants of the YAP1 gene, which should aid in the characterization of signaling differences among the potential protein products of the YAP1 gene. (C) 2012 Elsevier B.V. All rights reserved.

引用

页码：215 / 222

页数：8