Lau, B. et al. (2021) Human cytomegalovirus RNA2.7 is required for upregulating multiple cellular genes to promote cell motility and viral spread late in lytic infection. Journal of Virology, 95(20), e00698-21. (doi: 10.1128/JVI.00698-21) (PMID:34346763) (PMCID:PMC8475523)
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Abstract
Long non-coding RNAs are frequently associated with broad modulation of gene expression and thus provide the cell with the ability to synchronize entire metabolic processes. We used transcriptomic approaches to investigate whether the most abundant human cytomegalovirus-encoded lncRNA, RNA2.7, has this characteristic. By comparing cells infected with wild-type virus (WT) with cells infected with RNA2.7 deletion mutants, RNA2.7 was implicated in regulating a large number of cellular genes late in lytic infection. Pathway analysis indicated that >100 of these genes are associated with promoting cell movement, and the ten most highly regulated of these were validated in further experiments. Morphological analysis and live cell tracking of WT- and RNA2.7 mutant-infected cells indicated that RNA2.7 is involved in promoting the movement and detachment of infected cells late in infection, and plaque assays using sparse cell monolayers indicated that RNA2.7 is also involved in promoting cell-to-cell spread of virus. Consistent with the observation that upregulated mRNAs are relatively A+U-rich, which is a trait associated with transcript instability, and that they are also enriched in motifs associated with mRNA instability, transcriptional inhibition experiments on WT- and RNA2.7 mutant-infected cells showed that four upregulated transcripts were longer-lived in the presence of RNA2.7. These findings demonstrate that RNA2.7 is required for promoting cell movement and viral spread late in infection and suggest that this may be due to general stabilization of A+U-rich transcripts.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Camiolo, Dr Salvatore and Gu, Dr Quan and Davison, Professor Andrew and Suarez, Dr Nicolas and Lau, Dr Betty and Loney, Mr Colin and Kerr, Ms Karen |
| Creator Roles: | Lau, B.Conceptualization, Project administration, Supervision, Data curation, Formal analysis, Investigation, Validation, Visualization, Writing – original draft, Writing – review and editing Davison, A. J.Conceptualization, Project administration, Supervision, Funding acquisition, Resources, Writing – original draft, Writing – review and editing Camiolo, S.Data curation, Formal analysis, Software, Writing – review and editing Gu, Q.Data curation, Formal analysis, Software Kerr, K.Investigation, Validation Suárez, N. M.Investigation Loney, C.Investigation |
| Authors: | Lau, B., Kerr, K., Camiolo, S., Nightingale, K., Gu, Q., Antrobus, R., Suárez, N. M., Loney, C., Stanton, R. J., Weekes, M. P., and Davison, A. J. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research |
| Journal Name: | Journal of Virology |
| Publisher: | American Society for Microbiology |
| ISSN: | 0022-538X |
| ISSN (Online): | 1098-5514 |
| Published Online: | 04 August 2021 |
| Copyright Holders: | Copyright © 2021 Lau et al. |
| First Published: | First published in Journal of Virology 95(20): e00698-21 |
| Publisher Policy: | Reproduced under a Creative Commons License |
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