Cargando…

Pseudouridylation of Epstein-Barr virus noncoding RNA EBER2 facilitates lytic replication

Epstein-Barr virus (EBV) expresses two highly abundant noncoding RNAs called EBV-encoded RNA 1 (EBER1) and EBER2, which are preserved in all clinical isolates of EBV, thus underscoring their essential function in the viral life cycle. Recent epitranscriptomics studies have uncovered a vast array of...

Descripción completa

Detalles Bibliográficos
Autores principales: Henry, Belle A., Marchand, Virginie, Schlegel, Brent T., Helm, Mark, Motorin, Yuri, Lee, Nara
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9745832/
https://www.ncbi.nlm.nih.gov/pubmed/36100352
http://dx.doi.org/10.1261/rna.079219.122
_version_ 1784849234510479360
author Henry, Belle A.
Marchand, Virginie
Schlegel, Brent T.
Helm, Mark
Motorin, Yuri
Lee, Nara
author_facet Henry, Belle A.
Marchand, Virginie
Schlegel, Brent T.
Helm, Mark
Motorin, Yuri
Lee, Nara
author_sort Henry, Belle A.
collection PubMed
description Epstein-Barr virus (EBV) expresses two highly abundant noncoding RNAs called EBV-encoded RNA 1 (EBER1) and EBER2, which are preserved in all clinical isolates of EBV, thus underscoring their essential function in the viral life cycle. Recent epitranscriptomics studies have uncovered a vast array of distinct RNA modifications within cellular as well as viral noncoding RNAs that are instrumental in executing their function. Here we show that EBER2 is marked by pseudouridylation, and by using HydraPsiSeq the modification site was mapped to a single nucleotide within the 3′ region of EBER2. The writer enzyme was identified to be the snoRNA-dependent pseudouridine synthase Dyskerin, which is the catalytic subunit of H/ACA small nucleolar ribonucleoprotein complexes, and is guided to EBER2 by SNORA22. Similar to other noncoding RNAs for which pseudouridylation has a positive effect on RNA stability, loss of EBER2 pseudouridylation results in a decrease in RNA levels. Furthermore, pseudouridylation of EBER2 is required for the prolific accumulation of progeny viral genomes, suggesting that this single modification in EBER2 is important for efficient viral lytic replication. Taken together, our findings add to the list of RNA modifications that are essential for noncoding RNAs to implement their physiological roles.
format Online
Article
Text
id pubmed-9745832
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Cold Spring Harbor Laboratory Press
record_format MEDLINE/PubMed
spelling pubmed-97458322023-11-01 Pseudouridylation of Epstein-Barr virus noncoding RNA EBER2 facilitates lytic replication Henry, Belle A. Marchand, Virginie Schlegel, Brent T. Helm, Mark Motorin, Yuri Lee, Nara RNA Article Epstein-Barr virus (EBV) expresses two highly abundant noncoding RNAs called EBV-encoded RNA 1 (EBER1) and EBER2, which are preserved in all clinical isolates of EBV, thus underscoring their essential function in the viral life cycle. Recent epitranscriptomics studies have uncovered a vast array of distinct RNA modifications within cellular as well as viral noncoding RNAs that are instrumental in executing their function. Here we show that EBER2 is marked by pseudouridylation, and by using HydraPsiSeq the modification site was mapped to a single nucleotide within the 3′ region of EBER2. The writer enzyme was identified to be the snoRNA-dependent pseudouridine synthase Dyskerin, which is the catalytic subunit of H/ACA small nucleolar ribonucleoprotein complexes, and is guided to EBER2 by SNORA22. Similar to other noncoding RNAs for which pseudouridylation has a positive effect on RNA stability, loss of EBER2 pseudouridylation results in a decrease in RNA levels. Furthermore, pseudouridylation of EBER2 is required for the prolific accumulation of progeny viral genomes, suggesting that this single modification in EBER2 is important for efficient viral lytic replication. Taken together, our findings add to the list of RNA modifications that are essential for noncoding RNAs to implement their physiological roles. Cold Spring Harbor Laboratory Press 2022-11 /pmc/articles/PMC9745832/ /pubmed/36100352 http://dx.doi.org/10.1261/rna.079219.122 Text en © 2022 Henry et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society https://creativecommons.org/licenses/by-nc/4.0/This article is distributed exclusively by the RNA Society for the first 12 months after the full-issue publication date (see http://rnajournal.cshlp.org/site/misc/terms.xhtml). After 12 months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) .
spellingShingle Article
Henry, Belle A.
Marchand, Virginie
Schlegel, Brent T.
Helm, Mark
Motorin, Yuri
Lee, Nara
Pseudouridylation of Epstein-Barr virus noncoding RNA EBER2 facilitates lytic replication
title Pseudouridylation of Epstein-Barr virus noncoding RNA EBER2 facilitates lytic replication
title_full Pseudouridylation of Epstein-Barr virus noncoding RNA EBER2 facilitates lytic replication
title_fullStr Pseudouridylation of Epstein-Barr virus noncoding RNA EBER2 facilitates lytic replication
title_full_unstemmed Pseudouridylation of Epstein-Barr virus noncoding RNA EBER2 facilitates lytic replication
title_short Pseudouridylation of Epstein-Barr virus noncoding RNA EBER2 facilitates lytic replication
title_sort pseudouridylation of epstein-barr virus noncoding rna eber2 facilitates lytic replication
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9745832/
https://www.ncbi.nlm.nih.gov/pubmed/36100352
http://dx.doi.org/10.1261/rna.079219.122
work_keys_str_mv AT henrybellea pseudouridylationofepsteinbarrvirusnoncodingrnaeber2facilitateslyticreplication
AT marchandvirginie pseudouridylationofepsteinbarrvirusnoncodingrnaeber2facilitateslyticreplication
AT schlegelbrentt pseudouridylationofepsteinbarrvirusnoncodingrnaeber2facilitateslyticreplication
AT helmmark pseudouridylationofepsteinbarrvirusnoncodingrnaeber2facilitateslyticreplication
AT motorinyuri pseudouridylationofepsteinbarrvirusnoncodingrnaeber2facilitateslyticreplication
AT leenara pseudouridylationofepsteinbarrvirusnoncodingrnaeber2facilitateslyticreplication