Transfer rnas as dynamic and critical regulators of cancer progression

ABSTRACT Transfer RNAs (tRNAs) have been historically viewed as non-dynamic adaptors that decode the genetic code into proteins. Recent work has uncovered dynamic regulatory roles for these

fascinating molecules. Advances in tRNA detection methods have revealed that specific tRNAs can become modulated upon DNA copy number and chromatin alterations and can also be perturbed by

oncogenic signalling and transcriptional regulators in cancer cells or the tumour microenvironment. Such alterations in the levels of specific tRNAs have been shown to causally impact cancer

progression, including metastasis. Moreover, sequencing methods have identified tRNA-derived small RNAs that influence various aspects of cancer progression, such as cell proliferation and

invasion, and could serve as diagnostic and prognostic biomarkers or putative therapeutic targets in various cancers. Finally, there is accumulating evidence, including from genetic models,

that specific tRNA synthetases — the enzymes responsible for charging tRNAs with amino acids — can either promote or suppress tumour formation. In this Review, we provide an overview of how

deregulation of tRNAs influences cancer formation and progression. Access through your institution Buy or subscribe This is a preview of subscription content, access via your institution

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FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS SNORNAS: FUNCTIONS AND MECHANISMS IN BIOLOGICAL PROCESSES, AND ROLES IN TUMOR PATHOPHYSIOLOGY Article Open access 12

May 2022 SMALL NON-CODING RNAS IN HUMAN CANCER: FUNCTION, CLINICAL UTILITY, AND CHARACTERIZATION Article 15 January 2021 ILLUMINATING THE NONCODING GENOME IN CANCER Article 14 September 2020

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Scholar  Download references ACKNOWLEDGEMENTS The authors thank the members of the Tavazoie laboratory for critically reading the manuscript and for their helpful suggestions and comments.

The authors apologize to all the scientists whose work could not be cited owing to space limitations. S.F.T. and A.M.P. were supported by grants from the National Cancer Institute of the

National Institutes of Health under award numbers R01CA257153, R35CA274446 and U54CA261701, as well as the Black Family Metastasis Center and the Breast Cancer Research Foundation. Molecular

graphics were performed with UCSF ChimeraX, developed by the Resource for Biocomputing, Visualization and Informatics at the University of California, San Francisco, with support from

National Institutes of Health R01-GM129325 and the Office of Cyber Infrastructure and Computational Biology, National Institute of Allergy and Infectious Diseases. AUTHOR INFORMATION AUTHORS

AND AFFILIATIONS * Laboratory of Systems Cancer Biology, The Rockefeller University, New York, NY, USA Alexandra M. Pinzaru & Sohail F. Tavazoie Authors * Alexandra M. Pinzaru View

author publications You can also search for this author inPubMed Google Scholar * Sohail F. Tavazoie View author publications You can also search for this author inPubMed Google Scholar

CONTRIBUTIONS The authors contributed equally to all aspects of the article. CORRESPONDING AUTHORS Correspondence to Alexandra M. Pinzaru or Sohail F. Tavazoie. ETHICS DECLARATIONS COMPETING

INTERESTS The authors declare no competing interests. PEER REVIEW PEER REVIEW INFORMATION _Nature Reviews Cancer_ thanks Pierre Close and the other, anonymous, reviewer(s) for their

contribution to the peer review of this work. ADDITIONAL INFORMATION PUBLISHER’S NOTE Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional

affiliations. RELATED LINKS RCSB PROTEIN DATA BANK: https://www.rcsb.org/ UCSF CHIMERAX SOFTWARE: https://www.rbvi.ucsf.edu/chimerax GLOSSARY * Argonaute 2 (AGO2) cleavage assay An in vitro

assay that uses recombinant AGO2 to show specific cleavage of target oligonucleotides. * Epistatic interactions Interactions between two or more genes that influence a particular phenotype.

* Lineage-negative haematopoietic stem and progenitor cells Immature blood cells that lack surface protein markers found on mature blood cells. * Rare codons Codons found with the lowest

frequency in genes compared with synonymous codons in the same group. * Ribosome An essential ribonucleoprotein complex that performs protein synthesis in cells. * Ribosome profiling A

technique that provides a snapshot of all ribosome-bound messenger RNAs in cells with codon-level resolution. * RNA polymerase III (Pol III). An RNA polymerase complex that translates short,

non-coding RNAs, including transfer RNAs, 5S ribosomal RNA, U6 small nuclear RNA, vault RNA and other small RNAs. * tRNA misacylation The charging of a transfer RNA with the wrong amino

acid, not the amino acid cognate to the anticodon of the transfer RNA. * Wobble pairing Non-Watson–Crick base pairing of the first anticodon nucleoside: inosine can pair with adenosine,

uridine or cytidine; guanosine can pair with cytidine or uridine; uridine can pair with adenosine or guanosine. RIGHTS AND PERMISSIONS Springer Nature or its licensor (e.g. a society or

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this article is solely governed by the terms of such publishing agreement and applicable law. Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Pinzaru, A.M., Tavazoie, S.F.

Transfer RNAs as dynamic and critical regulators of cancer progression. _Nat Rev Cancer_ 23, 746–761 (2023). https://doi.org/10.1038/s41568-023-00611-4 Download citation * Accepted: 28 July

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