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

TLDR

Persistent HBV or HCV infection drives most cases of cirrhosis and hepatocellular carcinoma, and small non‑coding RNAs are key mediators of virus‑host interactions. The authors performed unbiased high‑throughput sequencing of 14–40‑nt small RNAs from liver samples of Japanese patients with advanced hepatitis B or C and HCC. 30–35‑nt 5′ tRNA‑halves were the most abundant small RNAs in non‑malignant liver, markedly increased in chronic hepatitis, surpassed miRNA levels, but were reduced and compositionally altered in HCC, with HBV‑associated HCC 5′ tRH levels correlating with angiogenin expression.

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.