Similar Datasets
Project description:Small, compact genomes confer a selective advantage to viruses, yet human cytomegalovirus (HCMV) expresses the long non-coding RNAs (lncRNAs) RNA1.2, RNA2.7, RNA4.9, and RNA5.0. These lncRNAs account for majority of the viral transcriptome, but their functions remain largely unknown. Here, we showed that HCMV lncRNAs, except for RNA5.0, are required throughout the entire viral life cycle. Deletion of each lncRNA resulted in a decrease in viral progeny during lytic replication and failing to efficiently establish latent reservoirs and reactivate. Nanopore direct RNA sequencing of native lncRNA molecules revealed that each lncRNA exhibited a dynamic modification landscape, depending on the state of infection. Global analysis of the lncRNA interactome identified 32, 11, and 89 host factors that specifically bind to RNA1.2, RNA2.7, and RNA4.9, respectively. Moreover, 52 proteins commonly bound to the three lncRNAs were identified, including 11 antiviral immunity-related proteins. Our molecular analyses found that three lncRNAs are modified with N⁶-methyladenosine (m6A) and interact with m6A readers in all infection states. In-depth functional analysis revealed that m6A–mediated lncRNA stabilization as the key mechanism by which lncRNAs are maintained at high levels. Our study lays the groundwork for understanding viral lncRNA–mediated regulation of host-virus interaction throughout the HCMV life cycle.
2022-11-14 | PXD034587 | Pride
Project description:Small, compact genomes confer a selective advantage to viruses, yet human cyto-megalovirus (HCMV) expresses the long non-coding RNAs (lncRNAs); RNA1.2, RNA2.7, RNA4.9, and RNA5.0. Little is known about the function of these lncRNAs in the virus life cycle. Here, we dissected the functional and molecular landscape of HCMV lncRNAs. We found that HCMV lncRNAs occupy ~30 % and 50~60 % of to-tal and poly(A)+ viral transcriptome, respectively, throughout virus life cycle. RNA1.2, RNA2.7, and RNA4.9, the three abundantly expressed lncRNAs, appear to be es-sential in all infection states. Among these three lncRNAs, depletion of RNA2.7 and RNA4.9 results in the greatest defect in maintaining latent reservoir and promoting lytic replication, respectively. Moreover, we delineated the global post-transcriptional nature of HCMV lncRNAs by nanopore direct RNA sequencing and interactome analysis. We revealed that the lncRNAs are modified with N⁶-methyladenosine (m6A) and interact with m6A readers in all infection states. In-depth analysis demonstrated that m6A machineries stabilize HCMV lncRNAs, which could account for the over-whelming abundance of viral lncRNAs. Our study lays the groundwork for under-standing the viral lncRNA–mediated regulation of host-virus interaction throughout the HCMV life cycle.
2022-11-16 | GSE217713 | GEO
Project description:Small, compact genomes confer a selective advantage to viruses, yet human cyto-megalovirus (HCMV) expresses the long non-coding RNAs (lncRNAs); RNA1.2, RNA2.7, RNA4.9, and RNA5.0. Little is known about the function of these lncRNAs in the virus life cycle. Here, we dissected the functional and molecular landscape of HCMV lncRNAs. We found that HCMV lncRNAs occupy ~30 % and 50~60 % of to-tal and poly(A)+ viral transcriptome, respectively, throughout virus life cycle. RNA1.2, RNA2.7, and RNA4.9, the three abundantly expressed lncRNAs, appear to be es-sential in all infection states. Among these three lncRNAs, depletion of RNA2.7 and RNA4.9 results in the greatest defect in maintaining latent reservoir and promoting lytic replication, respectively. Moreover, we delineated the global post-transcriptional nature of HCMV lncRNAs by nanopore direct RNA sequencing and interactome analysis. We revealed that the lncRNAs are modified with N⁶-methyladenosine (m6A) and interact with m6A readers in all infection states. In-depth analysis demonstrated that m6A machineries stabilize HCMV lncRNAs, which could account for the over-whelming abundance of viral lncRNAs. Our study lays the groundwork for under-standing the viral lncRNA–mediated regulation of host-virus interaction throughout the HCMV life cycle.
2022-11-16 | GSE217710 | GEO
Project description:Functional and molecular dissection of viral lncRNAs throughout HCMV life cycle
| PRJNA900198 | ENA
Project description:Functional and molecular dissection of viral lncRNAs throughout HCMV life cycle [shortread]
| PRJNA900204 | ENA
Project description:Functional and molecular dissection of viral lncRNAs throughout HCMV life cycle [longread]
| PRJNA900202 | ENA
Project description:Small, compact genomes confer a selective advantage to viruses, yet human cytomegalovirus (HCMV) expresses the long non-coding RNAs (lncRNAs); RNA1.2, RNA2.7, RNA4.9, and RNA5.0. Little is known about the function of these lncRNAs in the virus life cycle. Here, we dissected the functional and molecular landscape of HCMV lncRNAs. We found that HCMV lncRNAs occupy ~ 30% and 50-60% of total and poly(A)+viral transcriptome, respectively, throughout virus life cycle. RNA1.2, RNA2.7, and RNA4.9, the three abundantly expressed lncRNAs, appear to be essential in all infection states. Among these three lncRNAs, depletion of RNA2.7 and RNA4.9 results in the greatest defect in maintaining latent reservoir and promoting lytic replication, respectively. Moreover, we delineated the global post-transcriptional nature of HCMV lncRNAs by nanopore direct RNA sequencing and interactome analysis. We revealed that the lncRNAs are modified with N6-methyladenosine (m6A) and interact with m6A readers in all infection states. In-depth analysis demonstrated that m6A machineries stabilize HCMV lncRNAs, which could account for the overwhelming abundance of viral lncRNAs. Our study lays the groundwork for understanding the viral lncRNA-mediated regulation of host-virus interaction throughout the HCMV life cycle.
| S-EPMC9652368 | biostudies-literature
Project description:There is a need for new effective antivirals, particularly in response to the development of antiviral drug resistance and emerging RNA viruses such as SARS-CoV-2. Plants are a significant source of structurally diverse bioactive compounds for drug discovery suggesting that plant-derived natural products could be developed as antiviral agents. This article reviews the antiviral activity of plant-derived natural products against RNA viruses, with a focus on compounds targeting specific stages of the viral life cycle. A range of plant extracts and compounds have been identified with antiviral activity, often against multiple virus families suggesting they may be useful as broad-spectrum antiviral agents. The antiviral mechanism of action of many of these phytochemicals is not fully understood and there are limited studies and clinical trials demonstrating their efficacy and toxicity in vivo. Further research is needed to evaluate the therapeutic potential of plant-derived natural products as antiviral agents.
| S-EPMC9544774 | biostudies-literature
Project description:Previous studies of the evolution of genes expressed at different life-cycle stages of Drosophila melanogaster have not been able to disentangle adaptive from nonadaptive substitutions when using nonsynonymous sites. Here, we overcome this limitation by combining whole-genome polymorphism data from D. melanogaster and divergence data between D. melanogaster and Drosophila yakuba. For the set of genes expressed at different life-cycle stages of D. melanogaster, as reported in modENCODE, we estimate the ratio of substitutions relative to polymorphism between nonsynonymous and synonymous sites (α) and then α is discomposed into the ratio of adaptive (ωa) and nonadaptive (ωna) substitutions to synonymous substitutions. We find that the genes expressed in mid- and late-embryonic development are the most conserved, whereas those expressed in early development and postembryonic stages are the least conserved. Importantly, we found that low conservation in early development is due to high rates of nonadaptive substitutions (high ωna), whereas in postembryonic stages it is due, instead, to high rates of adaptive substitutions (high ωa). By using estimates of different genomic features (codon bias, average intron length, exon number, recombination rate, among others), we also find that genes expressed in mid- and late-embryonic development show the most complex architecture: they are larger, have more exons, more transcripts, and longer introns. In addition, these genes are broadly expressed among all stages. We suggest that all these genomic features are related to the conservation of mid- and late-embryonic development. Globally, our study supports the hourglass pattern of conservation and adaptation over the life-cycle.
| S-EPMC6535812 | biostudies-literature
Project description:Widespread declines in Atlantic and Pacific salmon (Salmo salar and Oncorhynchus spp.) have tracked recent climate changes, but managers still lack quantitative projections of the viability of any individual population in response to future climate change. To address this gap, we assembled a vast database of survival and other data for eight wild populations of threatened Chinook salmon (O. tshawytscha). For each population, we evaluated climate impacts at all life stages and modeled future trajectories forced by global climate model projections. Populations rapidly declined in response to increasing sea surface temperatures and other factors across diverse model assumptions and climate scenarios. Strong density dependence limited the number of salmon that survived early life stages, suggesting a potentially efficacious target for conservation effort. Other solutions require a better understanding of the factors that limit survival at sea. We conclude that dramatic increases in smolt survival are needed to overcome the negative impacts of climate change for this threatened species.
| S-EPMC7892847 | biostudies-literature