Related Experiment Video

Updated: Sep 6, 2025

Characterizing RNA Modifications in Single Neurons Using Mass Spectrometry
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Characterizing RNA Modifications in Single Neurons Using Mass Spectrometry

Published on: April 21, 2022

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Mitochondrial RNA modifications shape metabolic plasticity in metastasis

Sylvain Delaunay1, Gloria Pascual2, Bohai Feng3,4

  • 1German Cancer Research Center - Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany.

Nature
|June 29, 2022
PubMed

Insights

Cancer cells use specific RNA modifications in mitochondria to fuel metastasis. Targeting mitochondrial mRNA translation offers a new therapeutic strategy to inhibit cancer spread.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Metabolic Plasticity

Background:

  • Metastatic cancers exhibit enhanced metabolic plasticity, but the mechanisms are not fully understood.
  • RNA modifications play crucial roles in cellular processes, including gene expression.

Purpose of the Study:

  • To investigate the role of NOP2/Sun RNA methyltransferase 3 (NSUN3)-dependent RNA modifications in driving cancer metastasis.
  • To elucidate the mechanisms by which mitochondrial mRNA translation fuels cancer cell invasion and dissemination.

Main Methods:

  • Analysis of 5-methylcytosine (m5C) and 5-formylcytosine (f5C) modifications in mitochondrial tRNA.
  • Assessment of cancer cell viability, glycolysis, mitochondrial function, and metastasis in m5C-deficient cells.
  • Identification of a mitochondria-driven gene signature in head and neck cancer patients.

Main Results:

  • NSUN3-dependent m5C modification at position 34 in mitochondrial tRNA is essential for oxidative phosphorylation and metastasis.
  • m5C-deficient oral cancer cells show impaired metabolic plasticity and reduced metastasis, despite normal primary tumor growth.
  • CD36-dependent tumor cells require mitochondrial m5C for invasion and dissemination.
  • A mitochondria-driven gene signature predicts metastasis and progression in head and neck cancer.

Conclusions:

  • Mitochondrial RNA modifications, specifically m5C, are critical regulators of cancer cell metabolic plasticity and metastasis.
  • Targeting mitochondrial mRNA translation presents a potential therapeutic strategy to inhibit cancer metastasis.

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