ELAC2, an Enzyme for tRNA Maturation, Plays a Role in the Cleavage of a Mature tRNA to Produce a tRNA-Derived RNA Fragment During Respiratory Syncytial Virus Infection

Eun-Jin Choi; Wenzhe Wu; Ke Zhang; Inhan Lee; In-Hoo Kim; Yong Sun Lee; Xiaoyong Bao

doi:10.3389/fmolb.2020.609732

ELAC2, an Enzyme for tRNA Maturation, Plays a Role in the Cleavage of a Mature tRNA to Produce a tRNA-Derived RNA Fragment During Respiratory Syncytial Virus Infection

Front Mol Biosci. 2021 Feb 2:7:609732. doi: 10.3389/fmolb.2020.609732. eCollection 2020.

Authors

Eun-Jin Choi¹, Wenzhe Wu¹, Ke Zhang², Inhan Lee³, In-Hoo Kim⁴, Yong Sun Lee⁴, Xiaoyong Bao^{1

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Affiliations

¹ Department of Pediatrics, The University of Texas Medical Branch, Galveston, TX, United States.
² Department of Chemistry, The University of Houston Clear Lake, Clear Lake, TX, United States.
³ miRcore, Ann Arbor, MI, United States.
⁴ Department of Cancer Biomedical Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Korea.
⁵ Sealy Center for Molecular Medicine, The University of Texas Medical Branch, Galveston, TX, United States.
⁶ The Institute of Translational Sciences, The University of Texas Medical Branch, Galveston, TX, United States.
⁷ The Institute for Human Infections and Immunity, The University of Texas Medical Branch, Galveston, TX, United States.

Abstract

Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infection in young children. However, effective treatment against RSV is unavailable. tRNA-derived RNA fragments (tRFs) are a recently discovered family of non-coding RNAs. We made an early observation that RSV infection causes significant induction of tRFs, which are mainly derived from the 5'-end of mature tRNAs (tRF5). However, their functions and biogenesis mechanism are not fully understood. Herein, we identified an enzyme responsible for the induction of a functional tRF5 derived from tRNA-Gln-CTG (tRF5-GlnCTG). We found that tRF5-GlnCTG promotes RSV replication and its induction, assessed by Northern blot and a new qRT-PCR-based method, is regulated by ribonuclease ELAC2. ELAC2-mediated tRF5 induction has never been reported. We also found that ELAC2 is associated with RSV N and NS1 proteins. Given the fact that tRF5-GlnCTG plays a role in RSV replication, the identification of ELAC2 being responsible for tRF5-GlnCTG induction could provide new insights into therapeutic strategy development against RSV infection.

Keywords: ELAC2; RSV; biogenesis; tRF; viral replication.

Abstract

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