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RNA editing is a post-transcriptional modification where a precursor mRNA (pre-mRNA) nucleotide sequence is changed by base insertion, deletion, or modification. The extent of RNA editing varies from a few hundred bases, in mitochondrial DNA of trypanosomes, to a just single base, in nuclear genes of mammals. Even a single base change in the pre-mRNA can convert a codon for one amino acid into the codon for another amino acid or a stop codon. This type of re-coding can significantly affect the...
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C-to-U RNA deamination is the driving force accelerating SARS-CoV-2 evolution.

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The APOBEC-mediated cytosine-to-uracil (C-to-U) deamination is the primary driver of SARS-CoV-2 mutations, with its rate accelerating over time. This viral evolution is influenced by RNA structure, impacting COVID-19 pandemic control.

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Area of Science:

  • Virology
  • Molecular Biology
  • Genetics

Background:

  • The COVID-19 pandemic is driven by the rapid mutation of SARS-CoV-2.
  • APOBEC-mediated cytosine-to-uracil (C-to-U) deamination is a significant mutation source in the SARS-CoV-2 genome.
  • The precise mutation rate of C-to-U deamination and its driving forces remain unclear.

Purpose of the Study:

  • To investigate the mutation rate of C-to-U deamination in SARS-CoV-2 compared to other mutation types.
  • To identify the molecular mechanisms and driving forces behind the high and increasing C-to-U mutation rate.
  • To understand the role of RNA structure in SARS-CoV-2 mutation and evolution.

Main Methods:

  • Analysis of time-course global population data of SARS-CoV-2.
  • Correlation analysis between mutation rates, genomic regions, and local RNA structures.
  • Application of a cascade model to explain the observed mutation rate dynamics.

Main Results:

  • C-to-U deamination exhibits the highest novel mutation rate among all types in SARS-CoV-2.
  • The C-to-U mutation rate is not constant but is increasing over time (du/dt > 0).
  • A less stable local RNA structure correlates with a higher rate of novel C-to-U mutations.

Conclusions:

  • The RNA structure of SARS-CoV-2 is the molecular basis for its high and accelerating C-to-U deamination rate.
  • This APOBEC-mediated deamination mechanism is a key driver of SARS-CoV-2 mutation, adaptation, and evolution.
  • Understanding this dynamic mutation rate is crucial for controlling the COVID-19 pandemic.