Evidence map›Paper›PMID 31329932›Full record

ArticleNucleic acids research2019

Mechanism of allosteric activation of human mRNA cap methyltransferase (RNMT) by RAM: insights from accelerated molecular dynamics simulations.

Juan A Bueren-Calabuig, Marcus G Bage, Victoria H Cowling, Andrei V Pisliakov

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
0.8field-weighted citation impact, top 29% 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

34 citing papers in PubMed, 35 citations in OpenAlex.

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  14. Deciphering the secret codes in NClinical and translational medicine · 2025
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  16. The role of m5C, m1A and m7G modifications in tumors of urinary system.Frontiers in cell and developmental biology · 2025
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  17. The Role of mRNA Modifications in Bone Diseases.International journal of biological sciences · 2025
    Review
  18. Review
  19. Review
  20. Regulations of mFrontiers of medicine · 2024
    Review
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

4 authors at 1 institution in 1 country.

Juan A Bueren-CalabuigComputational Biology, School of Life Sciences, University of Dundee, Dundee, DD1 5EH, UK.
Marcus G BageComputational Biology, School of Life Sciences, University of Dundee, Dundee, DD1 5EH, UK.
Victoria H CowlingCentre for Gene Regulation and Expression, School of Life Sciences, University of Dundee, Dundee, DD1 5EH, UK.
Andrei V PisliakovComputational Biology, School of Life Sciences, University of Dundee, Dundee, DD1 5EH, UK.
University of Dundee · GB

Funding

Medical Research Council MR/K024213/1
6 · The paper itself

Abstract

The RNA guanine-N7 methyltransferase (RNMT) in complex with RNMT-activating miniprotein (RAM) catalyses the formation of a N7-methylated guanosine cap structure on the 5' end of nascent RNA polymerase II transcripts. The mRNA cap protects the primary transcript from exonucleases and recruits cap-binding complexes that mediate RNA processing, export and translation. By using microsecond standard and accelerated molecular dynamics simulations, we provide for the first time a detailed molecular mechanism of allosteric regulation of RNMT by RAM. We show that RAM selects the RNMT active site conformations that are optimal for binding of substrates (AdoMet and the cap), thus enhancing their affinity. Furthermore, our results strongly suggest the likely scenario in which the cap binding promotes the subsequent AdoMet binding, consistent with the previously suggested cooperative binding model. By employing the network community analyses, we revealed the underlying long-range allosteric networks and paths that are crucial for allosteric regulation by RAM. Our findings complement and explain previous experimental data on RNMT activity. Moreover, this study provides the most complete description of the cap and AdoMet binding poses and interactions within the enzyme's active site. This information is critical for the drug discovery efforts that consider RNMT as a promising anti-cancer target.

Indexed as

Allosteric RegulationAmino Acid SequenceBinding SitesCloning, MolecularEscherichia coliGene ExpressionGenetic VectorsHumansKineticsMethyltransferasesMolecular Dynamics SimulationProtein BindingProtein Conformation, alpha-HelicalProtein Conformation, beta-StrandProtein Interaction Domains and MotifsRecombinant ProteinsMethyltransferasesmRNA (guanine(N7))-methyltransferaseRAMAC protein, humanRecombinant ProteinsRNA-Binding ProteinsRNA CapsRNA Polymerase IIS-AdenosylhomocysteineS-Adenosylmethionine

Identifiers

PMID31329932
PMCPMC7145595
OpenAlexW2962753264

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.