title: Identification of primary equilibrative nucleoside transporter 1 mRNA isoforms resulting from alternative promoter usage in human hepatocytes.
abstract: Human equilibrative nucleoside transporter 1 (hENT1) transports various nucleoside analogues into cells. Although the single hENT1 promoter region (P1) and the mRNA isoform (a1) have been characterized previously, we have recently identified additional promoter regions P2 and P3 (which primarily generate c1/2/3 mRNAs and d1/2/3/4 mRNAs, respectively) in the human liver. Therefore, this study aimed at identifying the primary hENT1 mRNA isoforms expressed in human hepatocytes, while simultaneously obtaining functional evidence of alternative hENT1 promoter usage. Our results showed that the expressions of hENT1c1, d3, and (to a lesser extent) c2 mRNAs were strikingly predominant over the other mRNA isoforms in human hepatocytes, that the abundant expression of these mRNAs was consistent with the high levels of P2 and P3 promoter activity, and that these promoters were significantly marked by transcriptionally active histone modification in hepatic cells. To summarize, our results demonstrate that, resulting from the manipulated alternative promoter usage, hENT1c1 and d3 (and c2) mRNAs are primarily expressed in human hepatocytes, which suggests that they may play important roles in controlling hENT1 expression levels in those cells. Our findings are expected to provide significant insights into the molecular machinery of hENT1 expression control.
authors: Laboratory of Pharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, Chiba University.
authors: Tomomi
authors: T
authors: Furihata
authors: Misa
authors: M
authors: Mizuguchi
authors: Yuki
authors: Y
authors: Suzuki
authors: Shogo
authors: S
authors: Matsumoto
authors: Kaoru
authors: K
authors: Kobayashi
authors: Kan
authors: K
authors: Chiba
mesh_terms: D002460:Cell Line; D033721:Equilibrative Nucleoside Transporter 1 / Q000235:genetics*; D005786:Gene Expression Regulation / Q000235:genetics*; D022781:Hepatocytes / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D006801:Humans; D011401:Promoter Regions, Genetic / Q000235:genetics*; D059368:RNA Isoforms / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics
chemical_list: D033721:Equilibrative Nucleoside Transporter 1; D006657:Histones; D059368:RNA Isoforms; C438649:SLC29A1 protein, human