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

Sep 30, 2026

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Transfer RNAs (tRNAs) carry chemical modifications that affect stability and function, including adenosine-to-inosine (A-to-I) editing at anticodon position A34. The tRNA editing complex ADAT2/3 catalyzes this modification and expands wobble-position decoding. The study shows ADAT2/3 genes are commonly amplified or overexpressed across tumor types, including liposarcoma, where ADAT2/3 editing activity supports cell growth and tumorigenicity.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages25

Reading Time1 h 3 min

AccessFree to download

Abstract

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Introduction

Author Manuscr ipt Author Manuscr ipt Author Manuscr ipt Author Manuscript | | HHS Public Access
Author manuscript
J Mol Biol. Author manuscript; available in PMC 2026 January 09. | | --- | --- | Published in final edited form as: J Mol Biol. 2025 November 01; 437(21): 169414. doi:10.1016/j.jmb.2025.169414 . The tRNA Editing Complex ADAT2/3 Promotes Cancer Cell Growth and Codon-biased mRNA Translation☆ Julia Ramirez-Moya 1,2,3 , Titi Rindi Antika 1,2,3,4 , Qi Liu 1,2,3,5,6 , Xushen Xiong 1,2,3,7 , Raja Ali2 , Alejandro Gutierrez2,8,9 , Richard I. Gregory 1,2,3,4,8,10 1Stem Cell Program, Boston Children’s Hospital, Boston, MA 02115, USA 2 Division of Hematology/Oncology, Boston Children’s Hospital, Boston, MA 02115, USA 3 Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA 4Molecular, Cell, and Cancer Biology Department, UMass Chan Medical School, Worcester, MA 01605, USA 5 Rice Research Institute, Guangdong Academy of Agricultural Sciences, Guangzhou 510640 Guangdong Province, China 6Guangdong Key Laboratory of New Technology in Rice Breeding, Guangzhou 510640 Guangdong Province, China 7Zhejiang University Medical Center, Hangzhou, Zhejiang Province, China 8 Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA 9 Department of Oncology, St. Jude Children’s Research Hospital, Memphis, TN, USA 10 Harvard Initiative for RNA Medicine, Boston, MA 02115, USA 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 isan important modification that expands anticodon-codon recognition at the wobble position and ☆This article is part of a special issue entitled: ‘tRNA modifications (2025)’ published in Journal of Molecular Biology. This is an open access article under the CC BY license ([https://creativecom-mons.org/licenses/by/4.0/](https://creativecom-mons.org/licenses/by/4.0/)). Correspondence to Richard I. Gregory: Stem Cell Program, Boston Children’s Hospital, Boston, MA 02115, USA. [richard.gregory1@umassmed.edu](richard.gregory1@umassmed.edu) (R.I. Gregory). DECLARATION OF COMPETING INTEREST The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:‘R.I.G. is a co-founder, scientific advisory board member, and equity holder of Redona Therapeutics (formerly 28/7 Therapeutics), and advisor to Alida Biosciences, and to O2nix Bio. The Gregory lab has received research funding from Sanofi, Astellas, and Ono. All other authors declare no competing interests.’. CRediT authorship contribution statement Julia Ramirez-Moya: Writing – original draft, Methodology, Investigation, Formal analysis, Data curation, Conceptualization. Titi Rindi Antika: Writing – review & editing, Formal analysis, Data curation. Qi Liu: Methodology, Formal analysis, Data curation. Xushen Xiong: Formal analysis, Data curation. Raja Ali: Methodology, Investigation, Formal analysis. Alejandro Gutierrez: Supervision, Project administration, Funding acquisition, Formal analysis, Conceptualization. Richard I. Gregory: Writing – review & editing, Writing – original draft, Supervision, Project administration, Funding acquisition, Formal analysis, Data curation, Conceptualization. Author Manuscr ipt Author Manuscr ipt Author Manuscr ipt Author Manuscript Ramirez-Moya et al. Page 2 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 editi

FAQs

What role does A-to-I tRNA editing at A34 play in translation?

A-to-I editing in the tRNA anticodon at position A34 expands anticodon–codon recognition at the wobble position, altering decoding and the balance between codon usage and tRNA availability.

How are ADAT2/3 related to cancer cell growth in this study?

Genes encoding the ADAT2/3 deaminase complex are commonly amplified or overexpressed in multiple tumor types, and liposarcoma growth and tumorigenicity depend on ADAT2/3 tRNA editing activity.

What happens when ADAT2 is depleted?

ADAT2 depletion decreases tRNA editing, causes defective translation of a subset of mRNAs, and leads to altered protein homeostasis, supporting the conclusion that ADAT2 promotes oncogenesis.

Sep 30, 2026

Uploaded by moss~