2021
DOI: 10.1126/science.abe8526
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A viral RNA hijacks host machinery using dynamic conformational changes of a tRNA-like structure

Abstract: A tricky mimicry RNA viruses use dynamic, multifunctional folded elements to hijack host cellular machinery. Bonilla et al . used cryo–electron microscopy (cryo-EM) to explore an RNA element from Brome mosaic virus that tricks host cell tyrosine transfer RNA synthetase (TyrRS) into adding a tyrosine to the viral genome’s 3′ end. Visualizing this RNA both in isolation and bound to a cellular TyrRS revealed a bound structure unlike the canonical transfer RNA L-like … Show more

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Cited by 48 publications
(54 citation statements)
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“…Of interest, some aaRSs have been revealed to target mRNAs through binding tRNA-like elements, suggesting a mode of mRNA regulation by aaRSs (Levi and Arava, 2019;Garin et al, 2021). In addition, RNA viruses can hijack host cellular machinery by mimicking the tRNA-like structure to trick host aaRSs (Bonilla et al, 2021). Although there has been no study to report the tRNA-like elements regulated by TARS2, HARS2 or EARS2, the investigation of the aaRSsmediated control of viruses or host mRNAs, as well as the function of tRNA-like structures will reveal novel molecular mechanisms for COVID-19.…”
Section: Discussionmentioning
confidence: 99%
“…Of interest, some aaRSs have been revealed to target mRNAs through binding tRNA-like elements, suggesting a mode of mRNA regulation by aaRSs (Levi and Arava, 2019;Garin et al, 2021). In addition, RNA viruses can hijack host cellular machinery by mimicking the tRNA-like structure to trick host aaRSs (Bonilla et al, 2021). Although there has been no study to report the tRNA-like elements regulated by TARS2, HARS2 or EARS2, the investigation of the aaRSsmediated control of viruses or host mRNAs, as well as the function of tRNA-like structures will reveal novel molecular mechanisms for COVID-19.…”
Section: Discussionmentioning
confidence: 99%
“…Parameters are described in Materials and Methods. As done previously ( 11 ), several rounds of 3D classification were performed to increase the quality of the maps, using a bad ab initio reconstruction (grey volume) as a “sink” for suboptimal particles (see Materials and Methods). Details of 3D classifications and final refinements are provided in Fig.…”
Section: Supplementary Materials Formentioning
confidence: 99%
“…Dynamic states may be observed using NMR, but detailed structural information is limited by the size of the RNA. Given the latest advances in the ability of cryo-electron microscopy (cryo-EM) to solve dynamic RNA-only structures (11)(12)(13), we reasoned that this technique may offer a way to directly observe the 3D structure of RNA folding intermediates, including misfolded states, that have been elusive to structural biology.…”
Section: Introductionmentioning
confidence: 99%
“…In the meantime, however, due to their distinct nature, 3×3 UCU/UCU and 2×2 CU/UC internal loop motifs provide unique druggable targets, which could be exploited for therapeutic use. Despite the recent advancements in studying RNA dynamics using NMR ( Liu et al, 2021 ) or cryo-EM ( Bonilla et al, 2021 ), capturing the conformational variability observed in these complex RNA internal loops without contributions from computational techniques is very challenging. Thus, computational studies along with experimental studies can provide the necessary information at atomistic levels.…”
Section: Introductionmentioning
confidence: 99%