Evidence map›Paper›PMID 29866852›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2018

A folded viral noncoding RNA blocks host cell exoribonucleases through a conformationally dynamic RNA structure.

Anna-Lena Steckelberg, Benjamin M Akiyama, David A Costantino, Tim L Sit, Jay C Nix, Jeffrey S Kieft

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.

0numbers the graph read from it
0cells of the map it votes in
55citing papers in PubMed
6.3field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

55 citing papers in PubMed, 117 citations in OpenAlex.

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  16. A Genetic Circuit Design for Targeted Viral RNA Degradation.Bioengineering (Basel, Switzerland) · 2023
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 4 institutions in 1 country.

Anna-Lena SteckelbergDepartment of Biochemistry and Molecular Genetics, School of Medicine, University of Colorado, Aurora, CO 80045.
Benjamin M AkiyamaDepartment of Biochemistry and Molecular Genetics, School of Medicine, University of Colorado, Aurora, CO 80045.
David A CostantinoDepartment of Biochemistry and Molecular Genetics, School of Medicine, University of Colorado, Aurora, CO 80045.
Tim L SitDepartment of Entomology and Plant Pathology, North Carolina State University, Raleigh, NC 27606.
Jay C NixMolecular Biology Consortium, Advanced Light Source, Lawrence Berkeley National Laboratory, Berkeley, CA 94720.
Jeffrey S KieftDepartment of Biochemistry and Molecular Genetics, School of Medicine, University of Colorado, Aurora, CO 80045; Jeffrey.Kieft@ucdenver.edu.
University of Colorado Anschutz Medical Campus · USUniversity of Colorado Denver · USLawrence Berkeley National Laboratory · USNorth Carolina State University · US

Funding

University of Colorado Cancer Center Support Grant - Lung Cancer Patient-Derived Xenografts with Autologous Human Immune SystemsP30CA046934 · NCI · UNIVERSITY OF COLORADO DENVER · PI James V Degregori · 1988 to 2026
$117.0M
Structure, function, and dynamics of viral RNAs and RNA-containing complexesR35GM118070 · NIGMS · UNIVERSITY OF COLORADO DENVER · PI Jeffrey S Kieft · 2016 to 2026
$10.6M
Mechanisms of viral RNA maturation by co-opting cellular exonucleasesR01AI133348 · NIAID · UNIVERSITY OF COLORADO DENVER · PI KIEFT, JEFFREY S · 2017 to 2025
$4.5M
Macromolecular X-ray Data Collection InstrumentationS10OD012033 · OD · UNIVERSITY OF COLORADO DENVER · PI CHURCHILL, MAIR E · 2014 to 2014
$421k
A pathogenic RNA that resists degradation: characterization of subgenomic flavivirus RNAF32GM117730 · NIGMS · UNIVERSITY OF COLORADO DENVER · PI AKIYAMA, BENJAMIN · 2016 to 2017
$116k
NCI NIH HHS P30 CA046934NIAID NIH HHS R01 AI133348NIGMS NIH HHS F32 GM117730NIGMS NIH HHS R35 GM118070NIH HHS S10 OD012033
6 · The paper itself

Abstract

Folded RNA elements that block processive 5' → 3' cellular exoribonucleases (xrRNAs) to produce biologically active viral noncoding RNAs have been discovered in flaviviruses, potentially revealing a new mode of RNA maturation. However, whether this RNA structure-dependent mechanism exists elsewhere and, if so, whether a singular RNA fold is required, have been unclear. Here we demonstrate the existence of authentic RNA structure-dependent xrRNAs in dianthoviruses, plant-infecting viruses unrelated to animal-infecting flaviviruses. These xrRNAs have no sequence similarity to known xrRNAs; thus, we used a combination of biochemistry and virology to characterize their sequence requirements and mechanism of stopping exoribonucleases. By solving the structure of a dianthovirus xrRNA by X-ray crystallography, we reveal a complex fold that is very different from that of the flavivirus xrRNAs. However, both versions of xrRNAs contain a unique topological feature, a pseudoknot that creates a protective ring around the 5' end of the RNA structure; this may be a defining structural feature of xrRNAs. Single-molecule FRET experiments reveal that the dianthovirus xrRNAs undergo conformational changes and can use "codegradational remodeling," exploiting the exoribonucleases' degradation-linked helicase activity to help form their resistant structure; such a mechanism has not previously been reported. Convergent evolution has created RNA structure-dependent exoribonuclease resistance in different contexts, which establishes it as a general RNA maturation mechanism and defines xrRNAs as an authentic functional class of RNAs.

Indexed as

3' Untranslated RegionsAnimalsBase SequenceExoribonucleasesFlavivirusHost-Pathogen InteractionsNucleic Acid ConformationRNA FoldingRNA StabilityRNA, Viral3' Untranslated RegionsExoribonucleasesRNA, Viralexoribonuclease resistancenoncoding RNA maturationRNA dynamicsRNA structuresingle-molecule FRET

Identifiers

PMID29866852
PMCPMC6016793
OpenAlexW2806346360

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.