title: Identification, basic characterization and evolutionary analysis of differentially spliced mRNA isoforms of human YAP1 gene.
abstract: 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.
authors.affiliation: Laboratory of Signal Transduction and Proteomic Profiling, Weis Center for Research, Geisinger Clinic, 100 North Academy Avenue, Danville, PA 17821-2608, USA.
authors.forename: Christian J
authors.initials: CJ
authors.lastname: Gaffney
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Oka
authors.forename: Virginia
authors.initials: V
authors.lastname: Mazack
authors.forename: Dror
authors.initials: D
authors.lastname: Hilman
authors.forename: Uri
authors.initials: U
authors.lastname: Gat
authors.forename: Tomoki
authors.initials: T
authors.lastname: Muramatsu
authors.forename: Johji
authors.initials: J
authors.lastname: Inazawa
authors.forename: Alicia
authors.initials: A
authors.lastname: Golden
authors.forename: David J
authors.initials: DJ
authors.lastname: Carey
authors.forename: Amjad
authors.initials: A
authors.lastname: Farooq
authors.forename: Gerard
authors.initials: G
authors.lastname: Tromp
authors.forename: Marius
authors.initials: M
authors.lastname: Sudol
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D017398:Alternative Splicing / Q000235:genetics*; D000595:Amino Acid Sequence; D019143:Evolution, Molecular; D005091:Exons / Q000235:genetics*; D006801:Humans; D016350:Leucine Zippers / Q000235:genetics*; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000235:genetics*; D059368:RNA Isoforms; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D010750:Phosphoproteins; D059368:RNA Isoforms; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins; C088374:YAP1 protein, human