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An equilibrium-dependent retroviral mRNA switch regulates translational recoding.
Brian Houck-Loomis1, Michael A Durney, Carolina Salguero
1Department of Biochemistry and Molecular Biophysics, Howard Hughes Medical Institute, Columbia University, New York, New York 10032, USA.
Nature
|November 29, 2011
Summary
Retroviruses precisely control protein levels using RNA recoding. A protonation-dependent switch in murine leukemia virus RNA regulates this process, maintaining a critical Gag to Gag-Pol protein ratio.
Area of Science:
- Molecular Biology
- Virology
- Structural Biology
Background:
- Retroviruses require precise Gag and Gag-Pol protein ratios for assembly.
- Translational recoding via ribosomal frameshifting or stop codon read-through achieves this ratio.
- The mechanism controlling recoding frequency remains elusive.
Purpose of the Study:
- To elucidate the mechanism behind retroviral translational recoding.
- To determine how cis RNA motifs regulate Gag to Gag-Pol protein ratios.
- To investigate the structural basis of murine leukemia virus recoding.
Main Methods:
- Nuclear Magnetic Resonance (NMR) spectroscopy to determine RNA structure.
- Analysis of protonation-dependent conformational switches.
- Correlation of RNA conformation with in vivo protein expression levels.
Main Results:
- The NMR structure of the murine leukemia virus recoding signal was solved.
- A protonation-dependent switch induces an active, read-through permissive conformation.
- This active conformation is populated at ~6% at physiological pH, matching in vivo protein ratios.
- The RNA utilizes chemo-mechanical coupling for precise read-through frequency control.
Conclusions:
- A novel equilibrium-based mechanism governs translational recoding in retroviruses.
- Protonation-dependent RNA conformational changes are key to maintaining Gag/Gag-Pol ratios.
- This mechanism may be broadly applicable to other translational recoding events, including frameshifting.
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