Human cytomegalovirus long noncoding RNA4.9 regulates viral DNA replication.
Viruses are known for their extremely compact genomes composed almost entirely of protein-coding genes. Nonetheless, four long noncoding RNAs (lncRNAs) are encoded by human cytomegalovirus (HCMV). Although these RNAs accumulate to high levels during lytic infection, their functions remain largely un...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2020-04-01
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| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1008390 |
| _version_ | 1819260827243380736 |
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| author | Julie Tai-Schmiedel Sharon Karniely Betty Lau Adi Ezra Erez Eliyahu Aharon Nachshon Karen Kerr Nicolás Suárez Michal Schwartz Andrew J Davison Noam Stern-Ginossar |
| author_facet | Julie Tai-Schmiedel Sharon Karniely Betty Lau Adi Ezra Erez Eliyahu Aharon Nachshon Karen Kerr Nicolás Suárez Michal Schwartz Andrew J Davison Noam Stern-Ginossar |
| author_sort | Julie Tai-Schmiedel |
| collection | DOAJ |
| description | Viruses are known for their extremely compact genomes composed almost entirely of protein-coding genes. Nonetheless, four long noncoding RNAs (lncRNAs) are encoded by human cytomegalovirus (HCMV). Although these RNAs accumulate to high levels during lytic infection, their functions remain largely unknown. Here, we show that HCMV-encoded lncRNA4.9 localizes to the viral nuclear replication compartment, and that its depletion restricts viral DNA replication and viral growth. RNA4.9 is transcribed from the HCMV origin of replication (oriLyt) and forms an RNA-DNA hybrid (R-loop) through its G+C-rich 5' end, which may be important for the initiation of viral DNA replication. Furthermore, targeting the RNA4.9 promoter with CRISPR-Cas9 or genetic relocalization of oriLyt leads to reduced levels of the viral single-stranded DNA-binding protein (ssDBP), suggesting that the levels of ssDBP are coupled to the oriLyt activity. We further identified a similar, oriLyt-embedded, G+C-rich lncRNA in murine cytomegalovirus (MCMV). These results indicate that HCMV RNA4.9 plays an important role in regulating viral DNA replication, that the levels of ssDBP are coupled to the oriLyt activity, and that these regulatory features may be conserved among betaherpesviruses. |
| first_indexed | 2024-12-23T19:32:05Z |
| format | Article |
| id | doaj.art-0435113fc0764014a407f313d31e4fb6 |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-12-23T19:32:05Z |
| publishDate | 2020-04-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-0435113fc0764014a407f313d31e4fb62022-12-21T17:33:52ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742020-04-01164e100839010.1371/journal.ppat.1008390Human cytomegalovirus long noncoding RNA4.9 regulates viral DNA replication.Julie Tai-SchmiedelSharon KarnielyBetty LauAdi EzraErez EliyahuAharon NachshonKaren KerrNicolás SuárezMichal SchwartzAndrew J DavisonNoam Stern-GinossarViruses are known for their extremely compact genomes composed almost entirely of protein-coding genes. Nonetheless, four long noncoding RNAs (lncRNAs) are encoded by human cytomegalovirus (HCMV). Although these RNAs accumulate to high levels during lytic infection, their functions remain largely unknown. Here, we show that HCMV-encoded lncRNA4.9 localizes to the viral nuclear replication compartment, and that its depletion restricts viral DNA replication and viral growth. RNA4.9 is transcribed from the HCMV origin of replication (oriLyt) and forms an RNA-DNA hybrid (R-loop) through its G+C-rich 5' end, which may be important for the initiation of viral DNA replication. Furthermore, targeting the RNA4.9 promoter with CRISPR-Cas9 or genetic relocalization of oriLyt leads to reduced levels of the viral single-stranded DNA-binding protein (ssDBP), suggesting that the levels of ssDBP are coupled to the oriLyt activity. We further identified a similar, oriLyt-embedded, G+C-rich lncRNA in murine cytomegalovirus (MCMV). These results indicate that HCMV RNA4.9 plays an important role in regulating viral DNA replication, that the levels of ssDBP are coupled to the oriLyt activity, and that these regulatory features may be conserved among betaherpesviruses.https://doi.org/10.1371/journal.ppat.1008390 |
| spellingShingle | Julie Tai-Schmiedel Sharon Karniely Betty Lau Adi Ezra Erez Eliyahu Aharon Nachshon Karen Kerr Nicolás Suárez Michal Schwartz Andrew J Davison Noam Stern-Ginossar Human cytomegalovirus long noncoding RNA4.9 regulates viral DNA replication. PLoS Pathogens |
| title | Human cytomegalovirus long noncoding RNA4.9 regulates viral DNA replication. |
| title_full | Human cytomegalovirus long noncoding RNA4.9 regulates viral DNA replication. |
| title_fullStr | Human cytomegalovirus long noncoding RNA4.9 regulates viral DNA replication. |
| title_full_unstemmed | Human cytomegalovirus long noncoding RNA4.9 regulates viral DNA replication. |
| title_short | Human cytomegalovirus long noncoding RNA4.9 regulates viral DNA replication. |
| title_sort | human cytomegalovirus long noncoding rna4 9 regulates viral dna replication |
| url | https://doi.org/10.1371/journal.ppat.1008390 |
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