Evidence map›Paper›PMID 26147969›Full record

ArticlePloS one2015

Alkbh8 Regulates Selenocysteine-Protein Expression to Protect against Reactive Oxygen Species Damage.

Lauren Endres, Ulrike Begley, Ryan Clark, Chen Gu, Agnieszka Dziergowska, Andrzej Małkiewicz, J Andres Melendez, Peter C Dedon, Thomas J Begley

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.

0numbers the graph read from it
0cells of the map it votes in
65citing papers in PubMed
3.0field-weighted citation impact, top 9% 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

65 citing papers in PubMed, 101 citations in OpenAlex.

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  13. Stress response regulation of mRNA translation: Implications for antioxidant enzyme expression in cancer.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Review
  14. tRNA modification enzyme-dependent redox homeostasis regulates synapse formation and memory.Proceedings of the National Academy of Sciences of the United States of America · 2024
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5 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

9 authors at 4 institutions in 3 countries.

Lauren EndresColleges of Nanoscale Science and Engineering, SUNY Polytechnic Institute, Albany, New York 12203, United States of America; RNA Institute and Cancer Research Center, University at Albany, State University of New York, Albany, New York 12222, United States of America.
Ulrike BegleyColleges of Nanoscale Science and Engineering, SUNY Polytechnic Institute, Albany, New York 12203, United States of America.
Ryan ClarkColleges of Nanoscale Science and Engineering, SUNY Polytechnic Institute, Albany, New York 12203, United States of America.
Chen GuDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States of America.
Agnieszka DziergowskaInstitute of Organic Chemistry, Lodz University of Technology, Lodz, Poland.
Andrzej MałkiewiczInstitute of Organic Chemistry, Lodz University of Technology, Lodz, Poland.
J Andres MelendezColleges of Nanoscale Science and Engineering, SUNY Polytechnic Institute, Albany, New York 12203, United States of America.
Peter C DedonDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States of America; Singapore-MIT Alliance for Research and Technology, CREATE, Singapore, Singapore; Center for Environmental Health Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States of America.
Thomas J BegleyColleges of Nanoscale Science and Engineering, SUNY Polytechnic Institute, Albany, New York 12203, United States of America; RNA Institute and Cancer Research Center, University at Albany, State University of New York, Albany, New York 12222, United States of America.
SUNY Polytechnic Institute · USMassachusetts Institute of Technology · USInstitute of Organic Chemistry · PLLodz University of Technology · PL

Funding

TOXICOLOGY CORE UNITP30ES002109 · NIEHS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI LEVINE, STUART S · 1985 to 2020
$25.6M
The Roles of Trm9 and tRNA Methylation in the DNA Damage ResponseR01ES015037 · NIEHS · STATE UNIVERSITY OF NEW YORK AT ALBANY · PI BEGLEY, THOMAS J · 2006 to 2010
$2.4M
RNA Modifications as Biomarkers of Environmental Stress and InflammationR01ES017010 · NIEHS · STATE UNIVERSITY OF NEW YORK AT ALBANY · PI BEGLEY, THOMAS J · 2009 to 2013
$2.1M
Translational Control of ROS ManagementR01ES024615 · NIEHS · SUNY POLYTECHNIC INSTITUTE · PI BEGLEY, THOMAS J · 2014 to 2018
$1.8M
Howard Hughes Medical InstituteNIEHS NIH HHS ES002109,NIEHS NIH HHS ES015037NIEHS NIH HHS ES017010),NIEHS NIH HHS P30 ES002109NIEHS NIH HHS R01 ES015037NIEHS NIH HHS R01 ES017010NIEHS NIH HHS R01 ES024615
6 · The paper itself

Abstract

Environmental and metabolic sources of reactive oxygen species (ROS) can damage DNA, proteins and lipids to promote disease. Regulation of gene expression can prevent this damage and can include increased transcription, translation and post translational modification. Cellular responses to ROS play important roles in disease prevention, with deficiencies linked to cancer, neurodegeneration and ageing. Here we detail basal and damage-induced translational regulation of a group of oxidative-stress response enzymes by the tRNA methyltransferase Alkbh8. Using a new gene targeted knockout mouse cell system, we show that Alkbh8-/- embryonic fibroblasts (MEFs) display elevated ROS levels, increased DNA and lipid damage and hallmarks of cellular stress. We demonstrate that Alkbh8 is induced in response to ROS and is required for the efficient expression of selenocysteine-containing ROS detoxification enzymes belonging to the glutathione peroxidase (Gpx1, Gpx3, Gpx6 and likely Gpx4) and thioredoxin reductase (TrxR1) families. We also show that, in response to oxidative stress, the tRNA modification 5-methoxycarbonylmethyl-2'-O-methyluridine (mcm5Um) increases in normal MEFs to drive the expression of ROS detoxification enzymes, with this damage-induced reprogramming of tRNA and stop-codon recoding corrupted in Alkbh8-/- MEFS. These studies define Alkbh8 and tRNA modifications as central regulators of cellular oxidative stress responses in mammalian systems. In addition they highlight a new animal model for use in environmental and cancer studies and link translational regulation to the prevention of DNA and lipid damage.

Indexed as

AlkB Homolog 8, tRNA MethyltransferaseAnimalsDNA DamageFibroblastsGene ExpressionGene Expression RegulationGlutathione PeroxidaseMiceMice, Inbred C57BLNeoplasmsOxidative StressProtein Processing, Post-TranslationalReactive Oxygen SpeciesRNA, TransferSelenocysteineThioredoxin-Disulfide Reductase5-methoxycarbonylmethyluridineALKBH8 protein, mouseAlkB Homolog 8, tRNA MethyltransferaseGlutathione PeroxidaseReactive Oxygen SpeciesRNA, TransferSelenocysteineThioredoxin-Disulfide ReductasetRNA MethyltransferasesUridine

Identifiers

PMID26147969
PMCPMC4492958
OpenAlexW1666212754

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.