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

• DOI: 10.1038/srep07675
• Publication Date: 2015-01-08T10:06:30Z
• Authors: 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
• Keywords: 0303 health sciences; Carcinoma, Hepatocellular; Base Sequence; Pan troglodytes; Sequence Analysis, RNA; Liver Neoplasms; Molecular Sequence Data; High-Throughput Nucleotide Sequencing; Ribonuclease, Pancreatic; Hepatitis C, Chronic; Real-Time Polymerase Chain Reaction; Article; 3. Good health; MicroRNAs; 03 medical and health sciences; Hepatitis B, Chronic; Liver; RNA, Transfer; Animals; Humans; Immunoprecipitation

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.