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,Xiaoyong Bao,In-Hoo Kim,Inhan Lee,Ke Zhang,Yong Sun Lee,Wenzhe Wu

doi:10.3389/fmolb.2020.609732

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.

Highlights

Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infections (RTI) in children (Pickles and DeVincenzo, 2015)
Based on our sncRNA sequencing data (Wang et al, 2013), tRF5GlnCTG is among the few tRNAderived RNA fragments (tRFs) whose relative sequencing frequency is more than 10‰ in RSV-infected samples
This study demonstrated that RSV-induced tRF5-GlnCTG is functional as it promotes RSV replication

Summary

Introduction

Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infections (RTI) in children (Pickles and DeVincenzo, 2015). It is associated with high morbidity and mortality in at-risk populations including premature infants, the elderly, and immunocompromised patients (Lanari et al, 2004; Falsey et al, 2005; Simon et al, 2007). Non-coding RNAs (ncRNAs) are RNAs, which are not translated into proteins They include small ncRNAs (sncRNAs, 200 nts), both of which have emerged as critical regulatory molecules for various physiological and pathological processes including infectious diseases (Palazzo and Lee, 2015; Romano et al, 2017; Chen et al, 2019; Piket et al, 2019). The top five induced tRF5s have been experimentally investigated, the functions of other RSV-induced tRFs have not been explored and regulatory molecular mechanisms underlying their induction and activities await the investigation

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Conclusion