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Kinetic discrimination of self/non-self RNA by the ATPase activity of RIG-I and MDA5

Overview of attention for article published in BMC Biology, July 2015
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  • Above-average Attention Score compared to outputs of the same age (56th percentile)

Mentioned by

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5 tweeters

Citations

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33 Dimensions

Readers on

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51 Mendeley
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Title
Kinetic discrimination of self/non-self RNA by the ATPase activity of RIG-I and MDA5
Published in
BMC Biology, July 2015
DOI 10.1186/s12915-015-0166-9
Pubmed ID
Authors

Jade Louber, Joanna Brunel, Emiko Uchikawa, Stephen Cusack, Denis Gerlier

Abstract

The cytoplasmic RIG-like receptors are responsible for the early detection of viruses and other intracellular microbes by activating the innate immune response mediated by type I interferons (IFNs). RIG-I and MDA5 detect virus-specific RNA motifs with short 5'-tri/diphosphorylated, blunt-end double-stranded RNA (dsRNA) and >0.5-2 kb long dsRNA as canonical agonists, respectively. However, in vitro, they can bind to many RNA species, while in cells there is an activation threshold. As SF2 helicase/ATPase family members, ATP hydrolysis is dependent on co-operative RNA and ATP binding. Whereas simultaneous ATP and cognate RNA binding is sufficient to activate RIG-I by releasing autoinhibition of the signaling domains, the physiological role of the ATPase activity of RIG-I and MDA5 remains controversial. A cross-analysis of a rationally designed panel of RNA binding and ATPase mutants and truncated receptors, using type I IFN promoter activation as readout, allows us to refine our understanding of the structure-function relationships of RIG-I and MDA5. RNA activation of RIG-I depends on multiple critical RNA binding sites in its helicase domain as confirmed by functional evidence using novel mutations. We found that RIG-I or MDA5 mutants with low ATP hydrolysis activity exhibit constitutive activity but this was fully reverted when associated with mutations preventing RNA binding to the helicase domain. We propose that the turnover kinetics of the ATPase domain enables the discrimination of self/non-self RNA by both RIG-I and MDA5. Non-cognate, possibly self, RNA binding would lead to fast ATP turnover and RNA disassociation and thus insufficient time for the caspase activation and recruitment domains (CARDs) to promote downstream signaling, whereas tighter cognate RNA binding provides a longer time window for downstream events to be engaged. The exquisite fine-tuning of RIG-I and MDA5 RNA-dependent ATPase activity coupled to CARD release allows a robust IFN response from a minor subset of non-self RNAs within a sea of cellular self RNAs. This avoids the eventuality of deleterious autoimmunity effects as have been recently described to arise from natural gain-of-function alleles of RIG-I and MDA5.

Twitter Demographics

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

Mendeley readers

The data shown below were compiled from readership statistics for 51 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 2 4%
Korea, Republic of 1 2%
Unknown 48 94%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 16 31%
Researcher 12 24%
Student > Doctoral Student 5 10%
Student > Master 5 10%
Student > Bachelor 3 6%
Other 5 10%
Unknown 5 10%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 19 37%
Agricultural and Biological Sciences 15 29%
Immunology and Microbiology 4 8%
Chemistry 3 6%
Medicine and Dentistry 1 2%
Other 1 2%
Unknown 8 16%

Attention Score in Context

This research output has an Altmetric Attention Score of 2. 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 29 July 2015.
All research outputs
#8,410,806
of 15,283,408 outputs
Outputs from BMC Biology
#1,003
of 1,302 outputs
Outputs of similar age
#97,580
of 235,840 outputs
Outputs of similar age from BMC Biology
#1
of 1 outputs
Altmetric has tracked 15,283,408 research outputs across all sources so far. This one is in the 43rd percentile – i.e., 43% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,302 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 19.1. This one is in the 20th percentile – i.e., 20% of its peers scored the same or lower than it.
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 235,840 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 56% of its contemporaries.
We're also able to compare this research output to 1 others from the same source and published within six weeks on either side of this one. This one has scored higher than all of them