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Published on: February 12, 2022
Mechanisms and implications of programmed translational frameshifting
1Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD, USA. dinman@umd.edu
Wiley Interdisciplinary Reviews. RNA
|June 21, 2012
Summary
Programmed ribosomal frameshifting (PRF) allows ribosomes to alter reading frames, crucial for viral protein synthesis and potentially regulating cellular gene expression via mRNA decay. This mechanism offers a promising target for developing new antiviral therapies.
Area of Science:
- Molecular Biology
- Genetics
- Virology
Background:
- Ribosomes maintain translational reading frames to synthesize polypeptides from genetic information.
- Cis-acting signals in messenger RNAs (mRNAs) fine-tune gene expression.
- Programmed ribosomal frameshifting (PRF) involves ribosomes shifting reading frames (-1 or +1 direction) at specific sequences.
Purpose of the Study:
- To explore the mechanisms and implications of programmed ribosomal frameshifting (PRF).
- To investigate the role of PRF in viral gene expression and its potential as an antiviral target.
- To examine the function of PRF signals in cellular mRNA regulation and decay pathways.
Main Methods:
- Analysis of ribosome pausing at 'slippery' sequences.
- Investigating kinetic partitioning rates between in-frame and out-of-frame codons.
- Reviewing studies on PRF in viral and cellular mRNA contexts.
Main Results:
- PRF mechanisms often involve ribosome pausing, influencing frameshifting at slippery sequences.
- Viruses utilize PRF for synthesizing correct protein ratios, essential for viral assembly.
- Emerging evidence suggests PRF signals primarily destabilize cellular mRNAs, regulating gene expression via decay pathways.
Conclusions:
- Programmed ribosomal frameshifting is a key mechanism in viral replication and a potential antiviral therapeutic target.
- PRF may serve a significant role in regulating cellular gene expression through mRNA destabilization.
- Noncoding RNAs might play a role in regulating PRF.
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