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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
Summary
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.
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