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Mechanisms and biomedical implications of -1 programmed ribosome frameshifting on viral and bacterial mRNAs

Natalia Korniy1, Ekaterina Samatova1, Maria M Anokhina2

  • 1Department of Physical Biochemistry, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.

FEBS Letters
|June 22, 2019
PubMed

Insights

Ribosome frameshifting, essential for viral protein production, is regulated by mRNA structure and tRNA availability. Understanding these mechanisms offers new avenues for antiviral therapies.

Area of Science:

  • Molecular Biology
  • Virology
  • Genetics

Background:

  • Ribosome frameshifting is a key mechanism for expressing proteins from specific mRNA sequences.
  • This process is facilitated by mRNA slippery sites and secondary structures, influencing translation accuracy.
  • Frameshifting is crucial for the life cycle of various viruses and bacterial genes.

Purpose of the Study:

  • To review recent advancements in understanding the mechanisms of -1 ribosome frameshifting.
  • To explore frameshifting in viral genes (IBV 1a/1b, HIV-1 gag-pol, SFV 6K) and bacterial genes (Escherichia coli dnaX).
  • To highlight the role of aminoacyl-tRNA availability in directing frameshifting routes.

Main Methods:

  • Literature review of studies on ribosome frameshifting.
  • Analysis of frameshifting mechanisms in selected viral and bacterial systems.
  • Examination of the influence of tRNA supply on frameshifting efficiency and routes.

Main Results:

  • Frameshifting efficiency and route are contingent on aminoacyl-tRNA availability.
  • Ribosomes can frameshift during tRNA translocation or decoding when aminoacyl-tRNAs are scarce.
  • Viruses utilize diverse frameshifting strategies and multiple slippery sites for regulated protein synthesis.

Conclusions:

  • TRNA pools play a critical role in regulating ribosome frameshifting events.
  • Insights into frameshifting mechanisms provide a basis for developing novel antiviral therapies.
  • Targeting frameshifting offers a promising strategy to control viral replication.
Keywords:
RNAtRNAframeshiftingprotein synthesisrecodingregulationribosometranslation

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