Gammaherpesvirus infection alters transfer RNA splicing and triggers tRNA cleavage

Aidan C Manning; Mahmoud M Bashir; Ariana R Jimenez; Heather E Upton; Kathleen Collins; Todd M Lowe; Jessica M Tucker

doi:10.1101/2024.02.16.580780

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Gammaherpesvirus infection alters transfer RNA splicing and triggers tRNA cleavage

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Gammaherpesvirus infection alters transfer RNA splicing and triggers tRNA cleavage

Aidan C Manning, Mahmoud M Bashir, Ariana R Jimenez, Heather E Upton, Kathleen Collins, Todd M Lowe and Jessica M Tucker

bioRxiv : the preprint server for biology

Cold Spring Harbor Laboratory

02/17/2024

DOI: 10.1101/2024.02.16.580780

PMCID: PMC10888928

PMID: 38405876

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https://doi.org/10.1101/2024.02.16.580780View

Preprint (Author's original)This preprint has not been evaluated by subject experts through peer review. Preprints may undergo extensive changes and/or become peer-reviewed journal articles. Open Access

Abstract

Transfer RNAs (tRNAs) are fundamental for both cellular and viral gene expression during viral infection. Moreover, mounting evidence supports a noncanonical role for tRNA cleavage products in the control of gene expression during diverse conditions of stress and infection. We previously reported that infection with the model murine gammaherpesvirus, MHV68, leads to altered tRNA transcription, suggesting that tRNA regulation may play an important role in mediating viral replication or the host response. To better understand how viral infection alters tRNA expression, we combined Ordered Two Template Relay (OTTR) with tRNA-specific bioinformatic software called tRAX to profile full-length tRNAs and fragmented tRNA-derived RNAs (tDRs) during infection with MHV68. We find that OTTR-tRAX is a powerful sequencing strategy for combined tRNA/tDR profiling and reveals that MHV68 infection triggers pre-tRNA and mature tRNA cleavage, resulting in the accumulation of specific tDRs. Fragments of virally-encoded tRNAs (virtRNAs), as well as virtRNA base modification signatures are also detectable during infection. We present evidence that tRNA splicing factors are involved in the biogenesis of MHV68-induced cleavage products from pre-tRNAs and, in the case of CLP1 kinase, impact infectious virus production. Our data offers new insights into the importance of tRNA processing during gammaherpesvirus infection.

Details

Title: Subtitle: Gammaherpesvirus infection alters transfer RNA splicing and triggers tRNA cleavage
Creators: Aidan C Manning - University of California, Santa Cruz
Mahmoud M Bashir - Department of Microbiology and Immunology, Carver College of Medicine, University of Iowa, Iowa City, IA, 52242, USA
Ariana R Jimenez - University of Iowa
Heather E Upton - University of California, Berkeley
Kathleen Collins - University of California, Berkeley
Todd M Lowe - University of California, Santa Cruz
Jessica M Tucker - University of Iowa
Resource Type: Preprint
Publication Details: bioRxiv : the preprint server for biology
DOI: 10.1101/2024.02.16.580780
PMID: 38405876
PMCID: PMC10888928
Publisher: Cold Spring Harbor Laboratory; United States
Grant note: R01 HG006753 / NHGRI NIH HHS P30 CA086862 / NCI NIH HHS
Language: English
Date posted: 02/17/2024
Academic Unit: Microbiology and Immunology
Record Identifier: 9984562760002771

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