Evidence map›Paper›PMID 40907939›Full record

ArticleJournal of molecular biology2025

The tRNA Editing Complex ADAT2/3 Promotes Cancer Cell Growth and Codon-biased mRNA Translation.

Julia Ramirez-Moya, Titi Rindi Antika, Qi Liu, Xushen Xiong, Raja Ali, Alejandro Gutierrez, Richard I Gregory

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of molecular biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Article
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

7 authors.

Julia Ramirez-MoyaStem Cell Program, Boston Children's Hospital, Boston, MA 02115, USA; Division of Hematology/Oncology, Boston Children's Hospital, Boston, MA 02115, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
Titi Rindi AntikaStem Cell Program, Boston Children's Hospital, Boston, MA 02115, USA; Division of Hematology/Oncology, Boston Children's Hospital, Boston, MA 02115, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA; Molecular, Cell, and Cancer Biology Department, UMass Chan Medical School, Worcester, MA 01605, USA.
Qi LiuStem Cell Program, Boston Children's Hospital, Boston, MA 02115, USA; Division of Hematology/Oncology, Boston Children's Hospital, Boston, MA 02115, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA; Rice Research Institute, Guangdong Academy of Agricultural Sciences, Guangzhou 510640 Guangdong Province, China; Guangdong Key Laboratory of New Technology in Rice Breeding, Guangzhou 510640 Guangdong Province, China.
Xushen XiongStem Cell Program, Boston Children's Hospital, Boston, MA 02115, USA; Division of Hematology/Oncology, Boston Children's Hospital, Boston, MA 02115, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA; Zhejiang University Medical Center, Hangzhou, Zhejiang Province, China.
Raja AliDivision of Hematology/Oncology, Boston Children's Hospital, Boston, MA 02115, USA.
Alejandro GutierrezDivision of Hematology/Oncology, Boston Children's Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA; Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Richard I GregoryStem Cell Program, Boston Children's Hospital, Boston, MA 02115, USA; Division of Hematology/Oncology, Boston Children's Hospital, Boston, MA 02115, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA; Molecular, Cell, and Cancer Biology Department, UMass Chan Medical School, Worcester, MA 01605, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA; Harvard Initiative for RNA Medicine, Boston, MA 02115, USA. Electronic address: richard.gregory1@umassmed.edu.

Funding

Role of the Epitranscriptome in CancerR35CA232115 · NCI · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI GREGORY, RICHARD I. · 2019 to 2025
$7.2M
NCI NIH HHS R35 CA232115
6 · The paper itself

Abstract

Transfer RNAs (tRNAs) are subject to various chemical modifications that influence their stability or function. Adenosine to Inosine (A-to-I) editing in the tRNA anticodon at position A34 is an important modification that expands anticodon-codon recognition at the wobble position and is required for normal mRNA translation. The relevance of tRNA editing in cancer remains unexplored. Here we show that the genes encoding the ADAT2/3 deaminase complex, responsible for A-to-I tRNA editing in humans, are commonly amplified and/or overexpressed in several tumor types including liposarcoma (LPS). We find that LPS cell growth and tumorigenicity is dependent on ADAT2/3 tRNA editing activity. Mechanistically, we find decreased tRNA editing upon ADAT2 depletion, defective translation of a subset of mRNAs, and altered protein homeostasis. Thus, ADAT2 promotes oncogenesis and the translation of growth promoting mRNAs that are enriched in NNC codons that lack cognate tRNAs and therefore depend on A-I tRNA editing for decoding and mRNA translation. Our results identify ADAT2/3 as a potential new cancer therapeutic target.

Indexed as

Adenosine DeaminaseCodonNeoplasmsProtein BiosynthesisRNA-Binding ProteinsRNA EditingRNA, MessengerRNA, TransferAnimalsCell Line, TumorCell ProliferationGene Expression Regulation, NeoplasticHumansMiceAdenosine DeaminaseCodonRNA-Binding ProteinsRNA, MessengerRNA, TransferADAT2ADAT3EditingInosinetRNA

Identifiers

PMID40907939
PMCPMC12788883

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Registered trials

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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.