title: MxA transcripts with distinct first exons and modulation of gene expression levels by single-nucleotide polymorphisms in human bronchial epithelial cells.
abstract: Myxovirus resistance A (MxA) is a major interferon (IFN)-inducible antiviral protein. Promoter single-nucleotide polymorphisms (SNPs) of MxA near the IFN-stimulated response element (ISRE) have been frequently associated with various viral diseases, including emerging respiratory infections. We investigated the expression profile of MxA transcripts with distinct first exons in human bronchial epithelial cells. For primary culture, the bronchial epithelium was isolated from lung tissues with different genotypes, and total RNA was subjected to real-time reverse transcription polymerase chain reaction. The previously reported MxA transcript (T1) and a recently registered transcript with a distinct 5' first exon (T0) were identified. IFN-β and polyinosinic-polycytidylic acid induced approximately 100-fold higher expression of the T1 transcript than that of the T0 transcript, which also had a potential ISRE motif near its transcription start site. Even without inducers, the T1 transcript accounted for approximately two thirds of the total expression of MxA, levels of which were significantly associated with its promoter and exon 1 SNPs (rs17000900, rs2071430, and rs464138). Our results suggest that MxA observed in respiratory viral infections is possibly dominated by the T1 transcript and partly influenced by relevant 5' SNPs.
authors.affiliation: Department of Respiratory Diseases, Research Institute, National Center for Global Health and Medicine, Toyama, Shinjuku-ku, Tokyo, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Noguchi
authors.forename: Minako
authors.initials: M
authors.lastname: Hijikata
authors.forename: Emi
authors.initials: E
authors.lastname: Hamano
authors.forename: Ikumi
authors.initials: I
authors.lastname: Matsushita
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Ito
authors.forename: Jun
authors.initials: J
authors.lastname: Ohashi
authors.forename: Takahide
authors.initials: T
authors.lastname: Nagase
authors.forename: Naoto
authors.initials: N
authors.lastname: Keicho
mesh_terms: D020121:5' Untranslated Regions; D001980:Bronchi / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005091:Exons; D019204:GTP-Binding Proteins / Q000235:genetics*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D005838:Genotype; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology; D064547:Myxovirus Resistance Proteins; D020641:Polymorphism, Single Nucleotide; D020545:Respiratory Mucosa / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D020121:5' Untranslated Regions; D007370:Interferon Type I; C579071:MX1 protein, human; D064547:Myxovirus Resistance Proteins; D019204:GTP-Binding Proteins