Rnase L reprograms translation by widespread mRNA turnover escaped by antiviral mRNAs
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ABSTRACT:
PROVIDER: PRJNA510831 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR8356470.fastq.gz | Fastqsanger.gz | |||
| SRR8356471.fastq.gz | Fastqsanger.gz | |||
| SRR8356472.fastq.gz | Fastqsanger.gz | |||
| SRR8356473.fastq.gz | Fastqsanger.gz | |||
| SRR8356474.fastq.gz | Fastqsanger.gz |
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Project description:In response to foreign and endogenous double-stranded RNA (dsRNA), protein kinase R (PKR) and ribonuclease L (RNase L) reprogram translation in mammalian cells. PKR inhibits translation initiation through eIF2 phosphorylation, which triggers stress granule (SG) formation and promotes translation of stress responsive mRNAs. The mechanisms of RNase L-driven translation repression, its contribution to SG assembly, and its regulation of dsRNA stress-induced mRNAs are unknown. We demonstrate that RNase L drives translational shut-off in response to dsRNA by promoting widespread turnover of mRNAs. This alters stress granule assembly and reprograms translation by only allowing for the translation of mRNAs resistant to RNase L degradation, including numerous antiviral mRNAs such as IFN- . Individual cells differentially activate dsRNA responses revealing variation that can affect cellular outcomes. This identifies bulk mRNA degradation and the resistance of antiviral mRNAs as the mechanism by which RNaseL reprograms translation in response to dsRNA.
2019-07-10 | GSE124144 | GEO
Project description:In response to foreign and endogenous double-stranded RNA (dsRNA), protein kinase R (PKR) and ribonuclease L (RNase L) reprogram translation in mammalian cells. PKR inhibits translation initiation through eIF2α phosphorylation, which triggers stress granule (SG) formation and promotes translation of stress responsive mRNAs. The mechanisms of RNase L-driven translation repression, its contribution to SG assembly, and its regulation of dsRNA stress-induced mRNAs are unknown. We demonstrate that RNase L drives translational shut-off in response to dsRNA by promoting widespread turnover of mRNAs. This alters stress granule assembly and reprograms translation by allowing translation of mRNAs resistant to RNase L degradation, including numerous antiviral mRNAs such as interferon (IFN)-β. Individual cells differentially activate dsRNA responses revealing variation that can affect cellular outcomes. This identifies bulk mRNA degradation and the resistance of antiviral mRNAs as the mechanism by which RNase L reprograms translation in response to dsRNA.
| S-EPMC6754297 | biostudies-literature
Project description:Ribonuclease L (RNase L) is activated as part of the innate immune response and plays an important role in the clearance of viral infections. When activated, it endonucleolytically cleaves both viral and host RNAs, leading to a global reduction in protein synthesis. However, it remains unknown how widespread RNA decay, and consequent changes in the translatome, promote the elimination of viruses. To study how this altered transcriptome is translated, we assayed the global distribution of ribosomes in RNase L activated human cells with ribosome profiling. We found that RNase L activation leads to a substantial increase in the fraction of translating ribosomes in ORFs internal to coding sequences (iORFs) and ORFs within 5’ and 3’ UTRs (uORFs and dORFs). Translation of these alternative ORFs was dependent on RNase L’s cleavage activity, suggesting that mRNA decay fragments are translated to produce short peptides that may be important for antiviral activity.
2021-01-18 | GSE158044 | GEO
Project description:Ribonuclease L (RNase L) is an antiviral endoribonuclease that triggers widespread degradation of cellular mRNAs. Here, we show that the degradation of cellular mRNA by RNase L is a conserved response to flaviviruses, including Zika virus (ZIKV), dengue virus serotype 2 (DENV-2), and West Nile virus (WNV). Quantitative mass spectrometry in response to dsRNA or ZIKV infection shows that RNase L broadly downregulates the cellular proteome, reducing proteins with short half-lives involved in cell cycle progression, cellular metabolism, and protein synthesis. The mRNAs encoded by interferon-stimulated genes (ISGs) evade mRNA decay by RNase L, allowing for protein synthesis of ISG-encoding mRNAs. However, RNase L dampens ISG protein synthesis by triggering a block in nuclear mRNA export and repressing RNAPII-mediated transcription at later times during the antiviral response. These findings implicate reprograming of the cellular proteome as primary means by which RNase L combats viral infection, tumorigenesis, and immune dysregulation.
2025-10-04 | MSV000099383 | MassIVE
Project description:We found that multilayered phosphorylation of human Tob2 modulates its PABP-binding ability to change global deadenylation and mRNA turnover, which in turn reprograms transcriptome to influence cell proliferation.
2020-08-26 | GSE149684 | GEO
Project description:We found that multilayered phosphorylation of human Tob2 modulates its PABP-binding ability to change global deadenylation and mRNA turnover, which in turn reprograms transcriptome to influence cell proliferation.
2020-08-26 | GSE137170 | GEO
Project description:To investigate the possible range of additional RNase P substrates in vivo a strand-specific, high-density microarray was used to analyze what RNA accumulates with a mutation in the catalytic RNA subunit of nuclear RNase P in Saccharomyces cerevisiae. A wide variety of noncoding RNAs were shown to accumulate, suggesting nuclear RNase P participates in the turnover of normally unstable nuclear RNAs. In some cases, the accumulated noncoding RNAs were shown to be antisense to transcripts that commensurately decreased in abundance. Pre-mRNAs containing introns also accumulated broadly, consistent with either compromised splicing or failure to efficiently turnover pre-mRNAs that do not enter the splicing pathway. Taken together with the high complexity of the nuclear RNase P holoenzyme and its relatively non-specific capacity to bind and cleave mixed sequence RNAs, these data suggest nuclear RNase P facilitates turnover of nuclear RNAs in addition to its role in pre-tRNA biogenesis.
2011-08-29 | E-MEXP-3140 | biostudies-arrayexpress
Project description:Type I interferons were discovered as the primary antiviral cytokines and are now known to serve critical functions in host defense against bacterial pathogens. Accordingly, established mediators of interferon antiviral activity may mediate previously unrecognized antibacterial functions. RNase-L is the terminal component of an RNA decay pathway that is an important mediator of interferon-induced antiviral activity. Here we identify a novel role for RNase-L in the host antibacterial response. RNase-L-/- mice exhibited a dramatic increase in mortality following challenge with Bacillus anthracis and Escherichia coli; this increased susceptibility was due to a compromised immune response resulting in increased bacterial load. Investigation of the mechanisms of RNase-L antibacterial activity indicated that RNase-L is required for the optimal induction of proinflammatory cytokines that play essential roles in host defense from bacterial pathogens. RNase-L also regulated the expression of the endolysosomal protease, cathepsin-E, and endosome-associated activities, that function to eliminate internalized bacteria and may contribute to RNase-L antimicrobial action. Our results reveal a unique role for RNase-L in the antibacterial response that is mediated through multiple mechanisms. As a regulator of fundamental components of the innate immune response, RNase-L represents a viable therapeutic target to augment host defense against diverse microbial pathogens.
2008-12-19 | GSE13530 | GEO
Project description:Type I interferons were discovered as the primary antiviral cytokines and are now known to serve critical functions in host defense against bacterial pathogens. Accordingly, established mediators of interferon antiviral activity may mediate previously unrecognized antibacterial functions. RNase-L is the terminal component of an RNA decay pathway that is an important mediator of interferon-induced antiviral activity. Here we identify a novel role for RNase-L in the host antibacterial response. RNase-L-/- mice exhibited a dramatic increase in mortality following challenge with Bacillus anthracis and Escherichia coli; this increased susceptibility was due to a compromised immune response resulting in increased bacterial load. Investigation of the mechanisms of RNase-L antibacterial activity indicated that RNase-L is required for the optimal induction of proinflammatory cytokines that play essential roles in host defense from bacterial pathogens. RNase-L also regulated the expression of the endolysosomal protease, cathepsin-E, and endosome-associated activities, that function to eliminate internalized bacteria and may contribute to RNase-L antimicrobial action. Our results reveal a unique role for RNase-L in the antibacterial response that is mediated through multiple mechanisms. As a regulator of fundamental components of the innate immune response, RNase-L represents a viable therapeutic target to augment host defense against diverse microbial pathogens. two strains: wildtype and knockout, three time points: untreated, 2hours, and 8hours. three replication for each group. Totally 18 samples.
2008-12-19 | E-GEOD-13530 | biostudies-arrayexpress
Project description:RNase Y is an essential endoribonuclease affecting global mRNA stability in Bacillus subtilis. We used high-resolution tiling arrays to analyze the effect of RNase Y depletion on RNA abundance covering the entire genome. The data confirm that this endoribonuclease plays a key role in initiating the decay of a large number of mRNAs as well as non coding RNAs. Comparison of the data with that of two other recent studies revealed very significant differences. About two thirds of the mRNAs upregulated following RNase Y depletion were different when compared to either one of these studies and only about 10% of were in common in all three studies.Our data confirmed already known RNase Y substrates and due to the precision and reproducibility of the profiles allows an exceptionally detailed view of the turnover of hundreds of new RNA substrates.
2013-01-15 | GSE38897 | GEO