Viral miRNA adaptor differentially recruits miRNAs to target mRNAs through alternative base-pairing
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ABSTRACT:
PROVIDER: PRJNA515932 | ENA |
REPOSITORIES: ENA
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Project description: Not available
| S-EPMC6763288 | biostudies-literature
Project description:The viral non-coding RNA HSUR2 regulates apoptosis by recruiting host microRNAs to host mRNAs encoding apoptotic factors. The mechanism whereby HSUR2 targets specific host mRNAs is unknown. Here we developed iRICC to identify sequences mediating RNA-RNA interactions in vivo between a single RNA of interest and its binding RNAs. Sequences that mediate HSUR2-mRNA interactions identified by iRICC-seq were functionally validated by mutational analyses. Unlike other small regulatory non-coding RNAs, HSUR2 does not contain a “seed” region responsible for interaction with most target mRNAs, but rather uses different sequences to bind to different targets. Our findings describe a mode of interaction that provides HSUR2 with flexibility both in target recognition and in the selection of trans-acting miRNAs that are recruited for target mRNA repression.
2019-09-27 | GSE125371 | GEO
Project description:Chromosome 3p monosomy is associated with a poor clinical outcome of patients with uveal melanoma. Since a copy of the tumor suppressor miR-16 gene is lost for these patients, we postulated that a 3p loss may reduce the miR-16 amount and activity, promoting RNA derepression and tumor burden (loss of brake effect) as observed in chronic lymphocytic leukemia. Unexpectedly, we found that miR-16 expression level is not decreased despite the 3p monosomy. In contrast, our results suggested that miR-16 activity is impaired in uveal melanoma. Here, we investigated the molecular mechanism explaining the sequestration of miR-16 by RNAs. By defining the miR-16 interactome, two genes sets have been highlighted, suggesting two divergent miR-16 functions. In addition to the canonical miR-16 targets such as CCND3 and CDC25A, we identified another set of miR-16-interacting RNAs called thereafter miR-16 sponges. miR-16 binds to these RNAs sponge without inducing their decay. Mechanistically, the miR-16/RNA non-canonical base-pairing promoted stability of mRNAs involved in cancer cell proliferation. The biological relevance has been challenged in uveal melanoma. We showed that patients with poor overall survival expressed higher levels of miR-16 sponges and canonical miR-16 targets. These results strongly suggested that miR-16 is no longer able to repress its targets and, in contrast, promotes RNA stability and protein expression of oncogenes. miR-16 activity assessment using our Sponge-signature discriminates the patient’s overall survival as efficiently as the current method based on copy number variations and driver mutations detection. To conclude, miRNA loss of function due miRNA sequestration seems to promote cancer burden by two combined events – “loss of brake and an acceleration”. Our results highlight the oncogenic role of the non-canonical base-pairing between miRNAs/mRNAs in uveal melanoma.
2022-10-05 | GSE180399 | GEO
Project description:Here we describe a new class of immunostimulatory short duplex RNAs that potently induce production of type I interferon (IFN-I), and particularly IFN-β, in a wide range ofhuman cell types via end-to-end dimerization, direct binding to RIG-I, and activation of the RIG-I/IRF3 pathway. These RNAs require a minimum of 20 base pairs, lack any sequence or structural characteristics of known immunostimulatory RNAs, and instead require a unique conserved sequence motif (sense strand: 5’-C, antisense strand: 3’-GGG) that mediates the self-assembly of end-to-end RNA dimers by Hoogsteen G-G base-pairing. The presence of terminal hydroxyl or monophosphate groups, blunt or overhanging ends, or terminal RNA or DNA bases also did not affect their ability to induce IFN-I production. Immune stimulation mediated by these duplex RNAs results in broad spectrum inhibition of infections by many respiratory viruses with pandemic potential, including SARS-CoV-2, SARS-CoV, MERS-CoV, and influenza A, as well as the common cold virus HCoV-NL63 in cell lines and in human Lung Chips that mimic organlevel lung pathophysiology. These novel immunostimulatory motifs potentially could be harnessed to create broad-spectrum antiviral therapeutics, but they should be avoided when designing siRNAs to minimize immunological side effects.
2022-09-01 | PXD027838 | Pride
Project description:Bacteria selectively consume some carbon sources over others through a regulatory mechanism termed catabolite repression. Here, we show that the base pairing RNA Spot 42 plays a broad role in catabolite repression in Escherichia coli by directly repressing genes involved in central and secondary metabolism, redox balancing, and the consumption of diverse non-preferred carbon sources. Many of the genes repressed by Spot 42 are transcriptionally activated by the global regulator CRP. Since CRP represses Spot 42, these regulators participate in a specific regulatory circuit called a multi-output feedforward loop. We found that this loop can reduce leaky expression of target genes in the presence of glucose and can maintain repression of target genes under changing nutrient conditions. Our results suggest that base pairing RNAs in feedforward loops can help shape the steady-state levels and dynamics of gene expression.
2011-01-01 | GSE24875 | GEO
Project description:Bacteria selectively consume some carbon sources over others through a regulatory mechanism termed catabolite repression. Here, we show that the base pairing RNA Spot 42 plays a broad role in catabolite repression in Escherichia coli by directly repressing genes involved in central and secondary metabolism, redox balancing, and the consumption of diverse non-preferred carbon sources. Many of the genes repressed by Spot 42 are transcriptionally activated by the global regulator CRP. Since CRP represses Spot 42, these regulators participate in a specific regulatory circuit called a multi-output feedforward loop. We found that this loop can reduce leaky expression of target genes in the presence of glucose and can maintain repression of target genes under changing nutrient conditions. Our results suggest that base pairing RNAs in feedforward loops can help shape the steady-state levels and dynamics of gene expression. MG1655 lacIq cells harboring the control vector pBRplac or the Spot 42-inducible vector pSpot42 were grown in LB to an ABS600 of ~0.4 and treated with 1 mM IPTG. After 7 min, total RNA was isolated using the hot phenol extraction procedure.
2011-01-01 | E-GEOD-24875 | biostudies-arrayexpress
Project description:PAIR-MaP visualizes RNA base pairing complexity in human and bacterial non-coding RNAs
| PRJNA557729 | ENA
Project description:Short duplex RNAs induce potent immunostimulation via Hoogsteen G-G base pairing-mediated dimerization
| PRJNA753532 | ENA
Project description:Here we describe a new class of immunostimulatory short duplex RNAs that potently induce production of type I interferon (IFN-I), and particularly IFN-β, in a wide range of human cell types via end-to-end dimerization, direct binding to RIG-I, and activation of the RIG-I/IRF3 pathway. These RNAs require a minimum of 20 base pairs, lack any sequence or structural characteristics of known immunostimulatory RNAs, and instead require a unique conserved sequence motif (sense strand: 5’-C, antisense strand: 3’-GGG) that mediates the self-assembly of end-to-end RNA dimers by Hoogsteen G-G base-pairing. The presence of terminal hydroxyl or monophosphate groups, blunt or overhanging ends, or terminal RNA or DNA bases also did not affect their ability to induce IFN-I production. Immune stimulation mediated by these duplex RNAs results in broad spectrum inhibition of infections by many respiratory viruses with pandemic potential, including SARS-CoV-2, SARS-CoV, MERS-CoV, and influenza A, as well as the common cold virus HCoV-NL63 in cell lines and in human Lung Chips that mimic organlevel lung pathophysiology. These novel immunostimulatory motifs potentially could be harnessed to create broad-spectrum antiviral therapeutics, but they should be avoided when designing siRNAs to minimize immunological side effects.
2021-08-12 | GSE181827 | GEO
Project description:In this study, we conducted a thermodynamic analysis of RNA helix stability in the Eco80 artificial cytoplasm, which mimics in vivo conditions. Eco80 contains 80% of Escherichia coli metabolites, with biological concentrations of metal ions including 2 mM free Mg2+ and 29 mM metabolite-chelated Mg2+. We determined a set of Watson-Crick free energy nearest-neighbor parameters in Eco80 and found that helices are less stable by ∆∆Go37 ~ 1 kcal/mol in comparison to the traditional 1 M NaCl condition. Analysis indicates that Eco80 reduces the stability of three nearest-neighbor pairs. We applied this information to update the nearest-neighbor model using the RNAstructure package. We determined that our in vivo-like corrections have minimal effects on the prediction of RNA secondary structures determined in vitro and in silico. In contrast, in vivo-like corrections markedly improve prediction of fractional RNA base pairing in E. coli, as benchmarked with in vivo RNA chemical probing data using both DMS and EDC. In summary, our thermodynamic and chemical probing analyses of RNA helices in Eco80 indicate that RNA secondary structures are less stable in cells than in artificially stable in vitro buffer conditions such as 1 M NaCl.
2023-09-14 | GSE233607 | GEO