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Related Concept Videos

Regulation of Expression at Multiple Steps01:23

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The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the...
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Translational regulation in prokaryotes ensures efficient protein synthesis by controlling ribosome access to mRNA. This regulation is mediated by secondary RNA structures, including translational riboswitches, RNA thermometers, and small RNAs (sRNAs), which respond to intracellular and environmental signals to modulate gene expression.Translational RiboswitchesRiboswitches in the leader region of mRNAs can regulate translation by altering the accessibility of the Shine-Dalgarno (SD) sequence,...
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One of the unique features of tRNA is the presence of modified bases. In some tRNAs, modified bases account for nearly 20% of the total bases in the molecule. Altogether, these unusual bases protect the tRNA from enzymatic degradation by RNases.
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Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
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Base complementarity between the three base pairs of mRNA codon and the tRNA anticodon is not a failsafe mechanism. Inaccuracies can range from a single mismatch to no correct base pairing at all. The free energy difference between the correct and nearly correct base pairs can be as small as 3 kcal/ mol. With complementarity being the only proofreading step, the estimated error frequency would be one wrong amino acid in every 100 amino acids incorporated. However, error frequencies observed in...
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Trm9-Catalyzed tRNA Modifications Regulate Global Protein Expression by Codon-Biased Translation.

Wenjun Deng1, I Ramesh Babu1, Dan Su1

  • 1Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.

Plos Genetics
|December 17, 2015
PubMed
Summary

Trm9 enzyme modifications on transfer RNAs (tRNAs) selectively control protein production from specific genes. Loss of these essential tRNA modifications impairs protein synthesis, particularly under stress.

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Area of Science:

  • Molecular Biology
  • Genetics
  • Biochemistry

Background:

  • Post-transcriptional modifications of transfer RNAs (tRNAs) are vital for translation accuracy and efficiency.
  • The precise impact of these modifications on global protein production is not fully understood.

Purpose of the Study:

  • To investigate the role of Trm9-catalyzed tRNA modifications (mcm5 and mcm5s2) in regulating protein expression.
  • To determine if these modifications influence the translation of genes enriched with specific codons (AGA and GAA).

Main Methods:

  • Quantitative proteomics was employed to analyze protein production.
  • Gene expression and protein expression biases were controlled for.
  • Ribosome pausing was assessed in yeast strains lacking specific tRNA modifications.

Main Results:

  • Loss of Trm9 selectively reduced the expression of proteins encoded by genes rich in AGA and GAA codons.
  • These codon types were found in clusters within transcripts, potentially influencing translation.
  • Proteins with increased ribosome pausing in Trm9-deficient yeast showed higher down-regulation and more AGA/GAA clusters.

Conclusions:

  • Trm9-catalyzed tRNA modifications are critical regulators of global protein synthesis.
  • These modifications ensure efficient translation of specific codons, impacting protein levels under normal and stress conditions.