title: Small tRNA-derived RNAs are increased and more abundant than microRNAs in chronic hepatitis B and C.
abstract: Persistent infections with hepatitis B virus (HBV) or hepatitis C virus (HCV) account for the majority of cases of hepatic cirrhosis and hepatocellular carcinoma (HCC) worldwide. Small, non-coding RNAs play important roles in virus-host interactions. We used high throughput sequencing to conduct an unbiased profiling of small (14-40 nts) RNAs in liver from Japanese subjects with advanced hepatitis B or C and hepatocellular carcinoma (HCC). Small RNAs derived from tRNAs, specifically 30-35 nucleotide-long 5' tRNA-halves (5' tRHs), were abundant in non-malignant liver and significantly increased in humans and chimpanzees with chronic viral hepatitis. 5' tRH abundance exceeded microRNA abundance in most infected non-cancerous tissues. In contrast, in matched cancer tissue, 5' tRH abundance was reduced, and relative abundance of individual 5' tRHs was altered. In hepatitis B-associated HCC, 5' tRH abundance correlated with expression of the tRNA-cleaving ribonuclease, angiogenin. These results demonstrate that tRHs are the most abundant small RNAs in chronically infected liver and that their abundance is altered in liver cancer.
authors.affiliation: 1] Bioinformatics and Computational Biology Curriculum, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America [2] Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America [3] Departments of Medicine and Microbiology &Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America [4] Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
authors.forename: Sara R
authors.initials: SR
authors.lastname: Selitsky
authors.affiliation: 1] Bioinformatics and Computational Biology Curriculum, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America [2] Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
authors.forename: Jeanette
authors.initials: J
authors.lastname: Baran-Gale
authors.affiliation: Department of Gastroenterology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Honda
authors.affiliation: 1] Departments of Medicine and Microbiology &Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America [2] Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Yamane
authors.affiliation: 1] Departments of Medicine and Microbiology &Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America [2] Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Masaki
authors.affiliation: Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
authors.forename: Emily E
authors.initials: EE
authors.lastname: Fannin
authors.affiliation: Department of Virology and Immunology, Texas Biomedical Research Institute and Southwest National Primate Research Center, San Antonio, Texas, United States of America.
authors.forename: Bernadette
authors.initials: B
authors.lastname: Guerra
authors.affiliation: Department of Gastroenterology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan.
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Shirasaki
authors.affiliation: Department of Gastroenterology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan.
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Shimakami
authors.affiliation: Department of Gastroenterology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Kaneko
authors.affiliation: Department of Virology and Immunology, Texas Biomedical Research Institute and Southwest National Primate Research Center, San Antonio, Texas, United States of America.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Lanford
authors.affiliation: 1] Departments of Medicine and Microbiology &Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America [2] Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
authors.forename: Stanley M
authors.initials: SM
authors.lastname: Lemon
authors.affiliation: 1] Bioinformatics and Computational Biology Curriculum, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America [2] Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America [3] Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
authors.forename: Praveen
authors.initials: P
authors.lastname: Sethupathy
mesh_terms: D000818:Animals; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000473:pathology; D019694:Hepatitis B, Chronic / Q000235:genetics* / Q000473:pathology; D019698:Hepatitis C, Chronic / Q000235:genetics* / Q000473:pathology; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D047468:Immunoprecipitation; D008099:Liver / Q000378:metabolism; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology; D035683:MicroRNAs / Q000737:chemistry / Q000378:metabolism; D008969:Molecular Sequence Data; D002679:Pan troglodytes / Q000378:metabolism; D012343:RNA, Transfer / Q000737:chemistry / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D012259:Ribonuclease, Pancreatic / Q000235:genetics; D017423:Sequence Analysis, RNA
chemical_list: D035683:MicroRNAs; D012343:RNA, Transfer; C046366:angiogenin; D012259:Ribonuclease, Pancreatic