De Novo RNA Synthesis by RNA-Dependent RNA Polymerase Activity of Telomerase Reverse Transcriptase

Abstract

RNA-dependent RNA polymerase (RdRP) plays key roles in RNA silencing to generate double-stranded RNAs. In model organisms, such as Caenorhabditis elegans and Neurospora crassa, two types of small interfering RNAs (siRNAs), primary siRNAs and secondary siRNAs, are expressed; RdRP produces secondary siRNAs de novo, without using either Dicer or primers, while primary siRNAs are processed by Dicer. We reported that human telomerase reverse transcriptase (TERT) has RdRP activity and produces endogenous siRNAs in a Dicer-dependent manner. However, de novo synthesis of siRNAs by human TERT has not been elucidated. Here we show that the TERT RdRP generates short RNAs that are complementary to template RNAs and have 5′-triphosphorylated ends, which indicates de novo synthesis of the RNAs. In addition, we confirmed short RNA synthesis by TERT in several human carcinoma cell lines and found that TERT protein levels are positively correlated with RdRP activity.

ACKNOWLEDGMENTS

This work was supported in part by the Project for Development of Innovative Research on Cancer Therapeutics (P-DIRECT), Japan Agency for Medical Research and Development (Kenkichi Masutomi), by the Takeda Science Foundation (Yoshiko Maida), and by a research grant of the Princess Takamatsu Cancer Research Fund (grant 13-24520; Yoshiko Maida).

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.