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Viral lncRNA upregulates multiple A+U-richViral lncRNA upregulates multiple A+U-rich transcripts to promote cell motility and viral dissemination transcripts to promote cell motility and viral dissemination

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 and proteomic approaches to investigate whether the most abundant human cytomegalovirus-encoded lncRNA, RNA2.7, has this characteristic. By comparing RNA2.7 deletion mutants with wild-type virus, RNA2.7 was found to regulate a large number of cellular genes late in infection. Pathway analysis indicated that >100 RNA2.7-regulated cellular genes are associated with promoting cell movement, and ten of the most highly regulated were verified in further experiments. Morphological analysis and live cell tracking showed that RNA2.7 promotes the movement and detachment of infected cells late in infection, and plaque assays using sparse cell monolayers demonstrated that RNA2.7 promotes cell-to-cell dissemination and spread of virus. Bioinformatic analysis indicated that RNA2.7-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. Experiments involving transcriptional inhibition showed that transcripts from four RNA2.7-regulated cellular genes were longer-lived in the presence of RNA2.7. These findings demonstrate that RNA2.7 promotes cell movement and viral dissemination late in infection and indicate that this may be due to general stabilization of A+U-rich transcripts.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human) Human Herpesvirus 5 Strain Merlin

SUBMITTER: Katie Nightingale

LAB HEAD: Andrew Davison

PROVIDER: PXD022277 | Pride | 2021-07-27

REPOSITORIES: Pride

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			Action	DRS
	HCMV_RNA2_7_peptides_forPRIDE.xlsx	Xlsx
	HCMV_RNA2_7_proteins_forPRIDE.xlsx	Xlsx
	HCMV_lncRNA_2.7_1.raw	Raw
	HCMV_lncRNA_2.7_10.raw	Raw
	HCMV_lncRNA_2.7_11.raw	Raw

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Viral lncRNA upregulates multiple A+U-richViral lncRNA upregulates multiple A+U-rich transcripts to promote cell motility and viral dissemination transcripts to promote cell motility and viral dissemination

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