Alteration of the Premature tRNA Landscape by Gammaherpesvirus Infection

ABSTRACT Transfer RNAs (tRNAs) are transcribed by RNA polymerase III (RNAPIII) and play a central role in decoding our genome, yet their expression and noncanonical function remain understudied. Many DNA tumor viruses enhance the activity of RNAPIII, yet whether infection alters tRNA expression is l...

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Autores principales: Jessica M. Tucker, Aaron M. Schaller, Ian Willis, Britt A. Glaunsinger
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Publicado: American Society for Microbiology 2020
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spelling oai:doaj.org-article:3ae6d43670d84006b40fcfceb3f5291f2021-11-15T15:55:43ZAlteration of the Premature tRNA Landscape by Gammaherpesvirus Infection10.1128/mBio.02664-202150-7511https://doaj.org/article/3ae6d43670d84006b40fcfceb3f5291f2020-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02664-20https://doaj.org/toc/2150-7511ABSTRACT Transfer RNAs (tRNAs) are transcribed by RNA polymerase III (RNAPIII) and play a central role in decoding our genome, yet their expression and noncanonical function remain understudied. Many DNA tumor viruses enhance the activity of RNAPIII, yet whether infection alters tRNA expression is largely unknown. Here, we present the first genome-wide analysis of how viral infection alters the tRNAome. Using a tRNA-specific sequencing method (DM-tRNA-seq), we find that the murine gammaherpesvirus MHV68 induces global changes in premature tRNA (pre-tRNA) expression, with 14% of tRNA genes upregulated more than 3-fold, indicating that differential tRNA gene induction is a characteristic of DNA virus infection. Elevated pre-tRNA expression corresponds to increased RNAPIII occupancy for the subset of tRNA genes tested; additionally, posttranscriptional mechanisms contribute to the accumulation of pre-tRNA species. We find increased abundance of tRNA fragments derived from pre-tRNAs upregulated by viral infection, suggesting that noncanonical tRNA cleavage is also affected. Furthermore, pre-tRNA accumulation, but not RNAPIII recruitment, requires gammaherpesvirus-induced degradation of host mRNAs by the virally encoded mRNA endonuclease muSOX. We hypothesize that depletion of pre-tRNA maturation or turnover machinery contributes to robust accumulation of full-length pre-tRNAs in infected cells. Collectively, these findings reveal pervasive changes to tRNA expression during DNA virus infection and highlight the potential of using viruses to explore tRNA biology. IMPORTANCE Viral infection can dramatically change the gene expression landscape of the host cell, yet little is known regarding changes in noncoding gene transcription by RNA polymerase III (RNAPIII). Among these are transfer RNAs (tRNAs), which are fundamental in protein translation, yet whose gene regulatory features remain largely undefined in mammalian cells. Here, we perform the first genome-wide analysis of tRNA expression changes during viral infection. We show that premature tRNAs accumulate during infection with the model gammaherpesvirus MHV68 as a consequence of increased transcription, but that transcripts do not undergo canonical maturation into mature tRNAs. These findings underscore how tRNA expression is a highly regulated process, especially during conditions of elevated RNAPIII activity.Jessica M. TuckerAaron M. SchallerIan WillisBritt A. GlaunsingerAmerican Society for MicrobiologyarticleRNA polymerase IIIgammaherpesvirustRNAMicrobiologyQR1-502ENmBio, Vol 11, Iss 6 (2020)
institution DOAJ
collection DOAJ
language EN
topic RNA polymerase III
gammaherpesvirus
tRNA
Microbiology
QR1-502
spellingShingle RNA polymerase III
gammaherpesvirus
tRNA
Microbiology
QR1-502
Jessica M. Tucker
Aaron M. Schaller
Ian Willis
Britt A. Glaunsinger
Alteration of the Premature tRNA Landscape by Gammaherpesvirus Infection
description ABSTRACT Transfer RNAs (tRNAs) are transcribed by RNA polymerase III (RNAPIII) and play a central role in decoding our genome, yet their expression and noncanonical function remain understudied. Many DNA tumor viruses enhance the activity of RNAPIII, yet whether infection alters tRNA expression is largely unknown. Here, we present the first genome-wide analysis of how viral infection alters the tRNAome. Using a tRNA-specific sequencing method (DM-tRNA-seq), we find that the murine gammaherpesvirus MHV68 induces global changes in premature tRNA (pre-tRNA) expression, with 14% of tRNA genes upregulated more than 3-fold, indicating that differential tRNA gene induction is a characteristic of DNA virus infection. Elevated pre-tRNA expression corresponds to increased RNAPIII occupancy for the subset of tRNA genes tested; additionally, posttranscriptional mechanisms contribute to the accumulation of pre-tRNA species. We find increased abundance of tRNA fragments derived from pre-tRNAs upregulated by viral infection, suggesting that noncanonical tRNA cleavage is also affected. Furthermore, pre-tRNA accumulation, but not RNAPIII recruitment, requires gammaherpesvirus-induced degradation of host mRNAs by the virally encoded mRNA endonuclease muSOX. We hypothesize that depletion of pre-tRNA maturation or turnover machinery contributes to robust accumulation of full-length pre-tRNAs in infected cells. Collectively, these findings reveal pervasive changes to tRNA expression during DNA virus infection and highlight the potential of using viruses to explore tRNA biology. IMPORTANCE Viral infection can dramatically change the gene expression landscape of the host cell, yet little is known regarding changes in noncoding gene transcription by RNA polymerase III (RNAPIII). Among these are transfer RNAs (tRNAs), which are fundamental in protein translation, yet whose gene regulatory features remain largely undefined in mammalian cells. Here, we perform the first genome-wide analysis of tRNA expression changes during viral infection. We show that premature tRNAs accumulate during infection with the model gammaherpesvirus MHV68 as a consequence of increased transcription, but that transcripts do not undergo canonical maturation into mature tRNAs. These findings underscore how tRNA expression is a highly regulated process, especially during conditions of elevated RNAPIII activity.
format article
author Jessica M. Tucker
Aaron M. Schaller
Ian Willis
Britt A. Glaunsinger
author_facet Jessica M. Tucker
Aaron M. Schaller
Ian Willis
Britt A. Glaunsinger
author_sort Jessica M. Tucker
title Alteration of the Premature tRNA Landscape by Gammaherpesvirus Infection
title_short Alteration of the Premature tRNA Landscape by Gammaherpesvirus Infection
title_full Alteration of the Premature tRNA Landscape by Gammaherpesvirus Infection
title_fullStr Alteration of the Premature tRNA Landscape by Gammaherpesvirus Infection
title_full_unstemmed Alteration of the Premature tRNA Landscape by Gammaherpesvirus Infection
title_sort alteration of the premature trna landscape by gammaherpesvirus infection
publisher American Society for Microbiology
publishDate 2020
url https://doaj.org/article/3ae6d43670d84006b40fcfceb3f5291f
work_keys_str_mv AT jessicamtucker alterationoftheprematuretrnalandscapebygammaherpesvirusinfection
AT aaronmschaller alterationoftheprematuretrnalandscapebygammaherpesvirusinfection
AT ianwillis alterationoftheprematuretrnalandscapebygammaherpesvirusinfection
AT brittaglaunsinger alterationoftheprematuretrnalandscapebygammaherpesvirusinfection
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