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Related Concept Videos

Improving Translational Accuracy02:07

Improving Translational Accuracy

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...
Coordination of Gene Expression Processes in Bacteria01:29

Coordination of Gene Expression Processes in Bacteria

The DNA replication, transcription, and translation processes are intricately coupled in bacteria, allowing efficient gene expression and rapid protein synthesis. While this physical and functional coordination is advantageous, it introduces challenges that bacteria overcome through specific regulatory mechanisms.Coupling of Replication, Transcription, and TranslationThe coupling of replication, transcription, and translation is a hallmark of bacterial gene expression. As the replisome unwinds...
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The large ribosomal subunit has several important structures essential to translation. These include the peptidyl transferase center (PTC) - which is the site where the peptide bond is formed - and a large, internal, water-filled tube through which the nascent polypeptide moves. This latter structure is called the Peptide Exit Tunnel, and it begins at the PTC and spans the body of the large ribosomal subunit. During translation, as the nascent polypeptide chain is synthesized, it passes through...
Translational Regulation01:29

Translational Regulation

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,...
Ribosome Profiling02:24

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Ribosome profiling or ribo-sequencing is a deep sequencing technique that produces a snapshot of active translation in a cell. It selectively sequences the mRNAs protected by ribosomes to get an insight into a cell’s translation landscape at any given point in time.
Applications of ribosome profiling
Ribosome profiling has many applications, including in vivo monitoring of translation inside a particular organ or tissue type and quantifying new protein synthesis levels.
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During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA.  Marilyn Kozak discovered that the sequence RCCAUGG (where R stands for...

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Genome-wide Quantification of Translation in Budding Yeast by Ribosome Profiling
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Ribosome collisions and translation efficiency: optimization by codon usage and mRNA destabilization.

Namiko Mitarai1, Kim Sneppen, Steen Pedersen

  • 1Center for Models of Life, Niels Bohr Institute, University of Copenhagen, Copenhagen, Denmark.

Journal of Molecular Biology
|July 16, 2008
PubMed
Summary

Ribosome collisions and queuing are inevitable during mRNA translation, significantly reducing efficiency. Cells minimize these issues through mRNA instability and optimized codon usage, balancing breakdown costs with translation gains.

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Area of Science:

  • Molecular Biology
  • Systems Biology
  • Biophysics

Background:

  • Multiple ribosomes translate individual messenger RNAs (mRNAs) with a few-second interval between initiations.
  • Ribosome speed is codon-dependent, and ribosome queuing is a proposed mechanism for in vivo translation data.
  • Understanding ribosome traffic dynamics is crucial for explaining mRNA translation efficiency.

Purpose of the Study:

  • To model the stochastic translation process as a traffic problem to analyze ribosome collisions and queuing.
  • To determine the initiation on-rate and ribosome occlusion time for Escherichia coli lacZ mRNA in vivo.
  • To investigate the consequences of ribosome collisions and queuing on natural mRNA translation efficiency.

Main Methods:

  • Stochastic modeling of the translation process, conceptualized as a traffic problem.
  • In vivo analysis of Escherichia coli lacZ mRNA translation dynamics.
  • Quantitative determination of ribosome initiation rates and occlusion periods.

Main Results:

  • Ribosome collisions and queuing are inevitable outcomes of stochastic translation, substantially reducing translation efficiency on natural mRNAs.
  • The initiation on-rate for Escherichia coli lacZ mRNA was determined to be 0.8 to 1.1 initiations/s.
  • A preceding ribosome was found to occlude initiation for 1 second.

Conclusions:

  • Cells employ strategies such as mRNA instability and selected codon usage at the mRNA start to minimize ribosome collisions.
  • The cost of mRNA breakdown is compensated by increased translation efficiency resulting from collision mitigation.
  • Stochastic translation mechanisms inherently lead to inefficiencies that cellular strategies aim to overcome.