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Related Concept Videos

Translation01:31

Translation

158.7K
Lesson: Translation
Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of...
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Translation01:31

Translation

21.4K
Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of Life
Proteins are...
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Translational Regulation01:29

Translational Regulation

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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,...
739
Leaky Scanning02:28

Leaky Scanning

5.8K
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...
5.8K
Improving Translational Accuracy02:07

Improving Translational Accuracy

15.3K
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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Genetic Screens02:46

Genetic Screens

5.8K
Genetic screens are tools used to identify genes and mutations responsible for phenotypes of interest. Genetic screens help identify individuals or a group of people at risk of developing  genetic diseases and help them with early intervention, targeted therapy, and reproductive options.
Forward genetic screens
Forward or “classical” genetic screens involve creating random mutations in an organism’s DNA using radiation, mutagens, or insertion of additional bases, which...
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Measurement of Specific Mycobacterial Mistranslation Rates with Gain-of-function Reporter Systems
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Translational Safety Genetics.

Priyasma Bhoumik1, Alberto Del Rio-Espinola1, Florian Hahne1

  • 11 Preclinical Safety, Translational Medicine, Novartis Institutes for Biomedical Research, Basel, Switzerland.

Toxicologic Pathology
|December 10, 2016
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Summary
This summary is machine-generated.

Translational safety genetics uses animal genome sequencing to improve drug discovery. Selecting appropriate animal models based on genetic profiles enhances preclinical toxicity studies and reduces animal use.

Keywords:
animal speciescynomolgus monkeygenetic variationgenomesafety geneticssequencingtoxicology

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Area of Science:

  • Pharmacogenomics
  • Translational Science
  • Drug Development

Background:

  • Genetic variations influence drug responses across species.
  • Inconsistent animal models lead to misleading preclinical data.
  • Advances in genomics aid in selecting appropriate animal models.

Purpose of the Study:

  • To highlight the role of translational safety genetics in drug discovery.
  • To emphasize the importance of genetic characterization in animal model selection.
  • To align preclinical studies with the 3Rs principles (replacement, reduction, refinement).

Main Methods:

  • Leveraging advances in genome sequencing for various animal species (rodent, canine, nonhuman primate, minipig).
  • Genotypic characterization of drug targets, off-target interactors, and metabolism/disposition pathways.
  • Utilizing genetic information to select optimal animal models for toxicity studies.

Main Results:

  • Improved ability to select appropriate animal species for preclinical drug toxicity studies.
  • Enhanced selection based on genotypic characterization of targets and metabolic pathways.
  • Reduced likelihood of inconclusive or misleading animal study outcomes.

Conclusions:

  • Translational safety genetics offers new avenues for drug discovery and development.
  • Genetic profiling of animal models is crucial for accurate preclinical safety assessment.
  • Considering animal genetic background refines interpretation of toxicity study outcomes.