Dysfunctional tRNA reprogramming and codon-biased translation in cancer.

Autor: Dedon PC; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Singapore-MIT Alliance for Research and Technology, Antimicrobial Resistance IRG, Campus for Research Excellence and Technological Enterprise, Singapore 138602, Singapore. Electronic address: pcdedon@mit.edu., Begley TJ; University at Albany, Department of Biological Sciences, Albany, NY 12222, USA; RNA Institute, University at Albany, Albany, NY 12222, USA. Electronic address: tbegley@albany.edu.
Jazyk: angličtina
Zdroj: Trends in molecular medicine [Trends Mol Med] 2022 Nov; Vol. 28 (11), pp. 964-978. Date of Electronic Publication: 2022 Oct 11.
DOI: 10.1016/j.molmed.2022.09.007
Abstrakt: Many cancers hijack translation to increase the synthesis of tumor-driving proteins, the messenger mRNAs of which have specific codon usage patterns. Termed 'codon-biased translation' and originally identified in stress response regulation, this mechanism is supported by diverse studies demonstrating how the 50 RNA modifications of the epitranscriptome, specific tRNAs, and codon-biased mRNAs are used by oncogenic programs to promote proliferation and chemoresistance. The epitranscriptome writers METTL1-WDR4, Elongator complex protein (ELP)1-6, CTU1-2, and ALKBH8-TRM112 illustrate the principal mechanism of codon-biased translation, with gene amplifications, increased RNA modifications, and enhanced tRNA stability promoting cancer proliferation. Furthermore, systems-level analyses of 34 tRNA writers and 493 tRNA genes highlight the theme of tRNA epitranscriptome dysregulation in many cancers and identify candidate tRNA writers, tRNA modifications, and tRNA molecules as drivers of pathological codon-biased translation.
Competing Interests: Declaration of interests None declared by authors.
(Copyright © 2022 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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