Evidence map›Paper›PMID 26304538›Full record

ArticleNucleic acids research2015

Discovery of an essential nucleotidylating activity associated with a newly delineated conserved domain in the RNA polymerase-containing protein of all nidoviruses.

Kathleen C Lehmann, Anastasia Gulyaeva, Jessika C Zevenhoven-Dobbe, George M C Janssen, Mark Ruben, Hermen S Overkleeft, Peter A van Veelen, Dmitry V Samborskiy, Alexander A Kravchenko, Andrey M Leontovich and 4 more

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 151 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
151citing papers in PubMed, 2 pooled it
9.9field-weighted citation impact, top 1% 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

151 citing papers in PubMed, 2 syntheses or guidelines pooled it, 246 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
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  12. Human coronaviruses: activation and antagonism of innate immune responses.Microbiology and molecular biology reviews : MMBR · 2025
    Review
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  17. Point mutations at specific sites of the nsp12-nsp8 interface dramatically affect the RNA polymerization activity of SARS-CoV-2.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  18. Article
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  20. SARS-CoV-2 biology and host interactions.Nature reviews. Microbiology · 2024
    Review

91 more citing papers are in PubMed but not listed here.

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

14 authors at 3 institutions in 2 countries.

Kathleen C LehmannDepartment of Medical Microbiology, Leiden University Medical Center, Leiden, 2300 RC, Leiden, The Netherlands.
Anastasia GulyaevaDepartment of Medical Microbiology, Leiden University Medical Center, Leiden, 2300 RC, Leiden, The Netherlands.
Jessika C Zevenhoven-DobbeDepartment of Medical Microbiology, Leiden University Medical Center, Leiden, 2300 RC, Leiden, The Netherlands.
George M C JanssenDepartment of Immunohematology and Blood transfusion, Leiden University Medical Center, Leiden, 2300 RC, Leiden, The Netherlands.
Mark RubenLeiden Institute of Chemistry, Leiden University, 2300 CC, Leiden, The Netherlands.
Hermen S OverkleeftLeiden Institute of Chemistry, Leiden University, 2300 CC, Leiden, The Netherlands.
Peter A van VeelenDepartment of Immunohematology and Blood transfusion, Leiden University Medical Center, Leiden, 2300 RC, Leiden, The Netherlands.
Dmitry V SamborskiyBelozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119899 Moscow, Russia.
Alexander A KravchenkoBelozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119899 Moscow, Russia.
Andrey M LeontovichBelozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119899 Moscow, Russia.
Igor A SidorovDepartment of Medical Microbiology, Leiden University Medical Center, Leiden, 2300 RC, Leiden, The Netherlands.
Eric J SnijderDepartment of Medical Microbiology, Leiden University Medical Center, Leiden, 2300 RC, Leiden, The Netherlands.
Clara C PosthumaDepartment of Medical Microbiology, Leiden University Medical Center, Leiden, 2300 RC, Leiden, The Netherlands.
Alexander E GorbalenyaDepartment of Medical Microbiology, Leiden University Medical Center, Leiden, 2300 RC, Leiden, The Netherlands Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119899 Moscow, Russia Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, 119899 Moscow, Russia a.e.gorbalenya@lumc.nl.
Leiden University Medical Center · NLLomonosov Moscow State University · RULeiden University · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

RNA viruses encode an RNA-dependent RNA polymerase (RdRp) that catalyzes the synthesis of their RNA(s). In the case of positive-stranded RNA viruses belonging to the order Nidovirales, the RdRp resides in a replicase subunit that is unusually large. Bioinformatics analysis of this non-structural protein has now revealed a nidoviral signature domain (genetic marker) that is N-terminally adjacent to the RdRp and has no apparent homologs elsewhere. Based on its conservation profile, this domain is proposed to have nucleotidylation activity. We used recombinant non-structural protein 9 of the arterivirus equine arteritis virus (EAV) and different biochemical assays, including irreversible labeling with a GTP analog followed by a proteomics analysis, to demonstrate the manganese-dependent covalent binding of guanosine and uridine phosphates to a lysine/histidine residue. Most likely this was the invariant lysine of the newly identified domain, named nidovirus RdRp-associated nucleotidyltransferase (NiRAN), whose substitution with alanine severely diminished the described binding. Furthermore, this mutation crippled EAV and prevented the replication of severe acute respiratory syndrome coronavirus (SARS-CoV) in cell culture, indicating that NiRAN is essential for nidoviruses. Potential functions supported by NiRAN may include nucleic acid ligation, mRNA capping and protein-primed RNA synthesis, possibilities that remain to be explored in future studies.

Indexed as

Binding SitesConserved SequenceEquartevirusGuanosineGuanosine TriphosphateManganeseNidoviralesNucleotidesNucleotidyltransferasesPhosphatesPolyproteinsProtein Structure, TertiaryRNA-Dependent RNA PolymeraseSevere acute respiratory syndrome-related coronavirusUridineUridine TriphosphateGuanosineGuanosine TriphosphateManganeseNucleotidesNucleotidyltransferasesPhosphatesPolyproteinsRNA-Dependent RNA PolymeraseUridineUridine TriphosphateViral Proteins

Identifiers

PMID26304538
PMCPMC4787807
OpenAlexW2117455984

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.