Evidence map›Paper›PMID 38778156›Full record

ArticleThe EMBO journal2024

The immune response to RNA suppresses nucleic acid synthesis by limiting ribose 5-phosphate.

Pushpak Bhattacharjee, Die Wang, Dovile Anderson, Joshua N Buckler, Eveline de Geus, Feng Yan, Galina Polekhina, Ralf Schittenhelm, Darren J Creek, Lawrence D Harris and 1 more

Erratum issuedAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The EMBO journal, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
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

3 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors.

Pushpak BhattacharjeeCentre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research and Department of Molecular and Translational Sciences, Monash University, Clayton, VIC, 3168, Australia.
Die WangCentre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research and Department of Molecular and Translational Sciences, Monash University, Clayton, VIC, 3168, Australia.ORCID http://orcid.org/0000-0001-7628-7309
Dovile AndersonDrug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, 3052, Australia.
Joshua N BucklerFerrier Research Institute, Victoria University of Wellington, Lower Hutt, 5010, New Zealand.ORCID http://orcid.org/0000-0002-4397-9947
Eveline de GeusCentre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research and Department of Molecular and Translational Sciences, Monash University, Clayton, VIC, 3168, Australia.ORCID http://orcid.org/0000-0003-4453-3805
Feng YanAustralian Centre for Blood Diseases, Department of Clinical Hematology, Monash University, Clayton, VIC, 3004, Australia.ORCID http://orcid.org/0000-0002-8848-1739
Galina PolekhinaDepartment of Epidemiology & Preventive Medicine, Monash University, Melbourne, VIC, 3004, Australia.
Ralf SchittenhelmMonash Proteomics & Metabolomics Facility, Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC, 3800, Australia.
Darren J CreekDrug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, 3052, Australia.
Lawrence D HarrisFerrier Research Institute, Victoria University of Wellington, Lower Hutt, 5010, New Zealand.ORCID http://orcid.org/0000-0002-4214-1018
Anthony J SadlerCentre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research and Department of Molecular and Translational Sciences, Monash University, Clayton, VIC, 3168, Australia. anthony.sadler@hudson.org.au.ORCID http://orcid.org/0000-0002-7970-8030

Funding

Endeavour Fund UOOX1904NHMRC 1043398NHMRC 1143839Perpetual Tructees CF07/2408
6 · The paper itself

Abstract

During infection viruses hijack host cell metabolism to promote their replication. Here, analysis of metabolite alterations in macrophages exposed to poly I:C recognises that the antiviral effector Protein Kinase RNA-activated (PKR) suppresses glucose breakdown within the pentose phosphate pathway (PPP). This pathway runs parallel to central glycolysis and is critical to producing NADPH and pentose precursors for nucleotides. Changes in metabolite levels between wild-type and PKR-ablated macrophages show that PKR controls the generation of ribose 5-phosphate, in a manner distinct from its established function in gene expression but dependent on its kinase activity. PKR phosphorylates and inhibits the Ribose 5-Phosphate Isomerase A (RPIA), thereby preventing interconversion of ribulose- to ribose 5-phosphate. This activity preserves redox control but decreases production of ribose 5-phosphate for nucleotide biosynthesis. Accordingly, the PKR-mediated immune response to RNA suppresses nucleic acid production. In line, pharmacological targeting of the PPP during infection decreases the replication of the Herpes simplex virus. These results identify an immune response-mediated control of host cell metabolism and suggest targeting the RPIA as a potential innovative antiviral treatment.

Indexed as

eIF-2 KinaseMacrophagesPentose Phosphate PathwayRibosemonophosphatesAldose-Ketose IsomerasesAnimalsMiceNucleic AcidsPhosphorylationPoly I-CRNAVirus ReplicationAldose-Ketose IsomeraseseIF-2 KinaseNucleic AcidsPoly I-Cribose-5-phosphateRibosemonophosphatesribosephosphate isomeraseRNAAntiviralImmunityMetabolismNucleotide BiosynthesisPKR (Protein Kinase RNA-Activated)PPP (Pentose Phosphate Pathway)RPIA (Ribose 5-Phosphate Isomerase A)

Identifiers

PMID38778156
PMCPMC11217295

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.