TY - JOUR
T1 - Identification, basic characterization and evolutionary analysis of differentially spliced mRNA isoforms of human YAP1 gene
AU - Gaffney, Christian J.
AU - Oka, Tsutomu
AU - Mazack, Virginia
AU - Hilman, Dror
AU - Gat, Uri
AU - Muramatsu, Tomoki
AU - Inazawa, Johji
AU - Golden, Alicia
AU - Carey, David J.
AU - Farooq, Amjad
AU - Tromp, Gerard
AU - Sudol, Marius
N1 - Funding Information:
We thank our colleagues Kristin Berger, Kieran Harvey, Nikos Tapinos and Greg Yochum for valuable comments on the first version of the manuscript. This work was supported by PA Breast Cancer Coalition Grants (# 60707 and # 920093 ) plus the Geisinger Clinic (to MS) and by funds from the National Institutes of Health (Grant# R01-GM083897 ) and the USylvester Braman Family Breast Cancer Institute to AF.
PY - 2012/11/10
Y1 - 2012/11/10
N2 - 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 the YAP1 gene, which should aid in the characterization of signaling differences among the potential protein products of the YAP1 gene.
AB - 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 the YAP1 gene, which should aid in the characterization of signaling differences among the potential protein products of the YAP1 gene.
KW - Alternative splicing
KW - Leucine zipper
KW - Quantitative RT-PCR
KW - WW domains
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U2 - 10.1016/j.gene.2012.08.025
DO - 10.1016/j.gene.2012.08.025
M3 - Article
C2 - 22939869
AN - SCOPUS:84866433774
VL - 509
SP - 215
EP - 222
JO - Gene
JF - Gene
SN - 0378-1119
IS - 2
ER -