Small tRNA-derived RNAs are increased and more abundant than microRNAs in chronic hepatitis B and C

Sara R Selitsky, Jeanette Baran-Gale, Masao Honda, Daisuke Yamane, Takahiro Masaki, Emily E Fannin, Bernadette Guerra, Takayoshi Shirasaki, Tetsuro Shimakami, Shuichi Kaneko, Robert E Lanford, Stanley M Lemon, Praveen Sethupathy

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)7675
JournalScientific Reports
Volume5
DOIs
Publication statusPublished - 2015

Keywords

  • Animals
  • Base Sequence
  • Carcinoma, Hepatocellular
  • Hepatitis B, Chronic
  • Hepatitis C, Chronic
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Immunoprecipitation
  • Liver
  • Liver Neoplasms
  • MicroRNAs
  • Molecular Sequence Data
  • Pan troglodytes
  • RNA, Transfer
  • Real-Time Polymerase Chain Reaction
  • Ribonuclease, Pancreatic
  • Sequence Analysis, RNA

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