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Assessment of Selective mRNA Translation in Mammalian Cells by Polysome Profiling
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Assessment of Selective mRNA Translation in Mammalian Cells by Polysome Profiling

Published on: October 28, 2014

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Dysfunctional tRNA reprogramming and codon-biased translation in cancer

Peter C Dedon1, Thomas J Begley2

  • 1Department 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.

Trends in Molecular Medicine
|October 14, 2022
PubMed

Insights

Cancer cells exploit codon-biased translation, altering messenger RNA patterns to boost tumor protein production. This mechanism, involving epitranscriptome modifications and specific tRNAs, promotes cancer growth and resistance to therapy.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Epigenetics

Background:

  • Cancers utilize altered translation to synthesize proteins that drive tumor growth.
  • Messenger RNAs (mRNAs) in tumors exhibit specific codon usage patterns, a phenomenon termed codon-biased translation.
  • This mechanism is linked to the epitranscriptome, transfer RNAs (tRNAs), and oncogenic programs promoting proliferation and chemoresistance.

Purpose of the Study:

  • To elucidate the role of codon-biased translation in cancer.
  • To investigate the contribution of epitranscriptome modifications and tRNAs in promoting cancer progression.
  • To identify key molecular players in pathological codon-biased translation.

Main Methods:

  • Analysis of epitranscriptome writers (e.g., METTL1-WDR4, Elongator complex proteins, CTU1-2, ALKBH8-TRM112).
  • Examination of gene amplifications, RNA modifications, and tRNA stability.
  • Systems-level analysis of tRNA writers and tRNA genes.

Main Results:

  • Epitranscriptome writers facilitate codon-biased translation, with associated gene amplifications, increased RNA modifications, and enhanced tRNA stability promoting cancer proliferation.
  • Dysregulation of the tRNA epitranscriptome is a common theme in many cancers.
  • Specific tRNA writers, tRNA modifications, and tRNA molecules are identified as drivers of pathological codon-biased translation.

Conclusions:

  • Codon-biased translation is a critical mechanism hijacked by cancers to promote proliferation and chemoresistance.
  • The epitranscriptome and tRNA machinery are key regulators of this process in oncogenesis.
  • Targeting components of the tRNA epitranscriptome offers potential therapeutic strategies for cancer treatment.
Keywords:
cancercodonepitranscriptomegene expressionsystems biologytRNA modificationstranslational regulation

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