Related Experiment Video
Updated: Aug 6, 2026

06:18
Measurement of Specific Mycobacterial Mistranslation Rates with Gain-of-function Reporter Systems
Published on: April 26, 2019
The ribosome's response to codon-anticodon mismatches
T Daviter1, K B Gromadski, M V Rodnina
1Institute of Physical Biochemistry, University of Witten/Herdecke, 58448 Witten, Germany
Biochimie
|May 24, 2006
Summary
The ribosome ensures accurate protein synthesis by precisely selecting transfer RNAs (tRNAs) based on messenger RNA (mRNA) codons. This process involves conformational changes in the ribosome
Area of Science:
- Molecular biology
- Biochemistry
- Genetics
Background:
- The ribosome is a complex molecular machine responsible for protein synthesis.
- Transfer RNA (tRNA) molecules carry amino acids to the ribosome and match them to messenger RNA (mRNA) codons.
- Accurate translation relies on the precise selection of cognate tRNAs by the ribosome.
Purpose of the Study:
- To review the mechanisms governing tRNA recognition and selection by the ribosome.
- To highlight recent advances in understanding the molecular interactions involved in translational fidelity.
Main Methods:
- This review synthesizes findings from various biochemical and structural studies.
- It examines the role of ribosome-tRNA interactions, including A-minor RNA interactions.
- Focuses on the conformational dynamics of the ribosomal decoding site.
Main Results:
- Ribosome contacts and A-minor RNA interactions are crucial for specific codon-anticodon recognition.
- The decoding site switches between 'accepting' and 'rejecting' conformations for rapid and accurate tRNA selection.
- Sensitivity to mismatches during forward reactions influences tRNA misreading, impacting translational accuracy.
Conclusions:
- Ribosome-mediated tRNA selection is a dynamic process involving specific molecular contacts and conformational states.
- Understanding these mechanisms is key to deciphering the fidelity of the translational machinery.
- This knowledge has implications for understanding genetic diseases and developing novel therapeutics.
Related Concept Videos
Mismatch Repair
Overview
tRNA Activation
Aminoacyl-tRNA synthetases are present in both eukaryotes and bacteria. Though eukaryotes have 20 different aminoacyl-tRNA synthetases to couple to 20 amino acids, many bacteria do not have genes for all of these aminoacyl-tRNA synthetases. Despite this, they still use all 20 amino acids to synthesize their proteins. For instance, some bacteria do not have the gene encoding the enzyme that couples glutamine with its partner tRNA. In these organisms, one enzyme adds glutamic acid to all of the...
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...
Leaky Scanning
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...
tRNA Activation
Aminoacyl-tRNA synthetases are present in both eukaryotes and bacteria. Though eukaryotes have 20 different aminoacyl-tRNA synthetases to couple to 20 amino acids, many bacteria do not have genes for all of these aminoacyl-tRNA synthetases. Despite this, they still use all 20 amino acids to synthesize their proteins. For instance, some bacteria do not have the gene encoding the enzyme that couples glutamine with its partner tRNA. In these organisms, one enzyme adds glutamic acid to all of the...
Mismatch Repair
Organisms are capable of detecting and fixing nucleotide mismatches that occur during DNA replication. This sophisticated process requires identifying the new strand and replacing the erroneous bases with correct nucleotides. Mismatch repair is coordinated by many proteins in both prokaryotes and eukaryotes.
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...

