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A Conserved Histidine in the RNA Sensor RIG-I Controls Immune Tolerance to N1-2′O-Methylated Self RNA

Overview of attention for article published in Immunity, July 2015
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About this Attention Score

  • In the top 5% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (95th percentile)
  • High Attention Score compared to outputs of the same age and source (89th percentile)

Mentioned by

news
4 news outlets
twitter
5 X users
patent
5 patents
wikipedia
1 Wikipedia page

Citations

dimensions_citation
223 Dimensions

Readers on

mendeley
276 Mendeley
citeulike
1 CiteULike
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Title
A Conserved Histidine in the RNA Sensor RIG-I Controls Immune Tolerance to N1-2′O-Methylated Self RNA
Published in
Immunity, July 2015
DOI 10.1016/j.immuni.2015.06.015
Pubmed ID
Authors

Christine Schuberth-Wagner, Janos Ludwig, Ann Kristin Bruder, Anna-Maria Herzner, Thomas Zillinger, Marion Goldeck, Tobias Schmidt, Jonathan L. Schmid-Burgk, Romy Kerber, Steven Wolter, Jan-Philip Stümpel, Andreas Roth, Eva Bartok, Christian Drosten, Christoph Coch, Veit Hornung, Winfried Barchet, Beate M. Kümmerer, Gunther Hartmann, Martin Schlee

Abstract

The cytosolic helicase retinoic acid-inducible gene-I (RIG-I) initiates immune responses to most RNA viruses by detecting viral 5'-triphosphorylated RNA (pppRNA). Although endogenous mRNA is also 5'-triphosphorylated, backbone modifications and the 5'-ppp-linked methylguanosine ((m7)G) cap prevent immunorecognition. Here we show that the methylation status of endogenous capped mRNA at the 5'-terminal nucleotide (N1) was crucial to prevent RIG-I activation. Moreover, we identified a single conserved amino acid (H830) in the RIG-I RNA binding pocket as the mediator of steric exclusion of N1-2'O-methylated RNA. H830A alteration (RIG-I(H830A)) restored binding of N1-2'O-methylated pppRNA. Consequently, endogenous mRNA activated the RIG-I(H830A) mutant but not wild-type RIG-I. Similarly, knockdown of the endogenous N1-2'O-methyltransferase led to considerable RIG-I stimulation in the absence of exogenous stimuli. Studies involving yellow-fever-virus-encoded 2'O-methyltransferase and RIG-I(H830A) revealed that viruses exploit this mechanism to escape RIG-I. Our data reveal a new role for cap N1-2'O-methylation in RIG-I tolerance of self-RNA.

X Demographics

X Demographics

The data shown below were collected from the profiles of 5 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 276 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Germany 2 <1%
Japan 1 <1%
United States 1 <1%
Korea, Republic of 1 <1%
Unknown 271 98%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 68 25%
Researcher 44 16%
Student > Bachelor 33 12%
Student > Master 32 12%
Student > Doctoral Student 11 4%
Other 29 11%
Unknown 59 21%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 74 27%
Agricultural and Biological Sciences 63 23%
Immunology and Microbiology 33 12%
Medicine and Dentistry 19 7%
Chemistry 7 3%
Other 21 8%
Unknown 59 21%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 44. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 14 December 2023.
All research outputs
#932,614
of 25,374,647 outputs
Outputs from Immunity
#823
of 4,816 outputs
Outputs of similar age
#11,163
of 276,422 outputs
Outputs of similar age from Immunity
#7
of 67 outputs
Altmetric has tracked 25,374,647 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 96th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 4,816 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 33.3. This one has done well, scoring higher than 82% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 276,422 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 95% of its contemporaries.
We're also able to compare this research output to 67 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 89% of its contemporaries.