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Exploring the Arginine Methylome by Nuclear Magnetic Resonance Spectroscopy
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Arginine Methylation Regulates Ribosome CAR Function.

Kristen Scopino1, Carol Dalgarno1, Clara Nachmanoff1

  • 1Department of Biology, Wesleyan University, Middletown, CT 06459, USA.

International Journal of Molecular Sciences
|February 12, 2021
PubMed
Summary
This summary is machine-generated.

Methylation of ribosomal protein Rps3 regulates translation. This modification weakens the CAR interaction surface, impacting how ribosomes bind mRNA codons during cellular stress.

Keywords:
A-site decoding centerarginine methylationcodon adjacencymRNA GCN periodicitymolecular dynamicsribosome translocationstress regulation

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Area of Science:

  • Molecular Biology
  • Structural Biology
  • Biochemistry

Background:

  • The ribosome's CAR (C1054, A1196, R146) interaction surface is proposed to regulate translation.
  • This surface may interact with the next mRNA codon (+1 codon) entering the ribosome's A site.
  • R146, a component of the CAR surface, can be methylated by Sfm1 methyltransferase.

Purpose of the Study:

  • To investigate the effect of R146 methylation on the CAR interaction surface.
  • To elucidate the mechanism by which R146 methylation impacts CAR function.
  • To understand how R146 methylation influences translation regulation in response to cellular stress.

Main Methods:

  • Molecular dynamics simulations were employed to analyze the CAR interaction surface.
  • The study focused on the structural and energetic consequences of R146 methylation.

Main Results:

  • Methylation of R146 compromises the CAR surface integrity by weakening cation-pi stacking between R146 and A1196.
  • This reduction in cation-pi stacking leads to decreased hydrogen-bonding between the CAR surface and the +1 mRNA codon.
  • Ribosomes with unmethylated R146, potentially found in stressed cells, exhibit enhanced CAR/+1 codon interactions.

Conclusions:

  • R146 methylation serves as a regulatory mechanism for the ribosome's CAR interaction surface.
  • The degree of R146 methylation influences the ribosome's ability to interact with the +1 mRNA codon.
  • This interaction modulation tunes translation levels, adapting cellular function to altered cellular contexts, particularly under stress.