title: Differential effects of a common splice site polymorphism on the generation of OAS1 variants in human bronchial epithelial cells.
abstract: The 2',5'-oligoadenylate synthetase 1 (OAS1) is one of the major interferon-inducible proteins and a critical component of the host defense system against viral infection. A single nucleotide polymorphism (SNP), rs10774671, presumably responsible for alternate splicing of this gene, has frequently been associated with a variety of viral diseases, including emerging respiratory infections. We investigated the SNP-dependent expression of OAS1 variants in primary cultured human bronchial epithelial cells. Total RNA was subjected to real-time RT-PCR with specific primer sets designed to amplify each transcript variant. We found that the p46 transcript was mainly expressed in cells with the GG genotype, whereas the p42 transcript was highly expressed, and the p44a (alternate exon in intron 5), p48, and p52 transcripts were expressed to a lesser extent, in cells with the AA genotype. Immunoblot analysis revealed that the p46 isoform and a smaller amount of the p42 isoform were present in cells with the GG genotype, whereas only the p42 isoform was clearly observed in cells with the AA genotype. Cellular DNA fragmentation induced by neutrophil elastase was more preferentially found in cells with the AA genotype. Thus, our findings provide insights into the potential role of OAS1 polymorphisms in respiratory infection.
authors.affiliation: Department of Respiratory Diseases, Research Institute, National Center for Global Health and Medicine, Tokyo 162-8655, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Noguchi
authors.forename: Emi
authors.initials: E
authors.lastname: Hamano
authors.forename: Ikumi
authors.initials: I
authors.lastname: Matsushita
authors.forename: Minako
authors.initials: M
authors.lastname: Hijikata
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Ito
authors.forename: Takahide
authors.initials: T
authors.lastname: Nagase
authors.forename: Naoto
authors.initials: N
authors.lastname: Keicho
mesh_terms: D015088:2',5'-Oligoadenylate Synthetase / Q000235:genetics* / Q000378:metabolism; D017398:Alternative Splicing; D001980:Bronchi / Q000166:cytology*; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005838:Genotype; D006801:Humans; D015151:Immunoblotting; D016899:Interferon-beta / Q000494:pharmacology; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D022821:RNA Splice Sites / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D007527:Isoenzymes; D022821:RNA Splice Sites; D016899:Interferon-beta; C475085:OAS1 protein, human; D015088:2',5'-Oligoadenylate Synthetase