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Related Concept Videos

Mutations01:39

Mutations

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Overview
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Mutations01:35

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Mutations are changes in the sequence of DNA. These changes can occur spontaneously or they can be induced by exposure to environmental factors. Mutations can be characterized in a number of different ways: whether and how they alter the amino acid sequence of the protein, whether they occur over a small or large area of DNA, and whether they occur in somatic cells or germline cells.
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Transfer RNA Synthesis02:36

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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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Single Nucleotide Polymorphisms-SNPs01:05

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A single nucleotide polymorphism or SNP is a single nucleotide variation at a specific genomic position in a large population. It is the most prevalent type of sequence variation found in the human genome. Point mutations that occur in more than 1% of the population qualify as SNPs. These are present once every 1000 nucleotides on an average in the human genome. Replacement of a purine with another purine (A/G) or a pyrimidine with another pyrimidine (C/T) is known as a transition. In contrast,...
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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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Translation01:31

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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.
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A Novel Saturation Mutagenesis Approach: Single Step Characterization of Regulatory Protein Binding Sites in RNA Using Phosphorothioates
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Silent Polymorphisms: Can the tRNA Population Explain Changes in Protein Properties?

Tamara Fernández-Calero1,2, Florencia Cabrera-Cabrera3, Ricardo Ehrlich4,5

  • 1Biochemistry-Molecular Biology, Facultad de Ciencias, Universidad de la República, Iguá 4225, Montevideo 11400, Uruguay. tamfer@pasteur.edu.uy.

Life (Basel, Switzerland)
|February 23, 2016
PubMed
Summary

Silent mutations, like the estrogen receptor alpha Ala87 polymorphism, impact protein function. Changes in transfer RNA (tRNA) abundance influence protein folding and cellular states in eukaryotes.

Keywords:
estrogen receptor alphaisoacceptor tRNAsprotein foldingsynonymous polymorphismstranslation kinetics

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Area of Science:

  • Molecular Biology
  • Genetics
  • Biochemistry

Background:

  • Silent mutations, or synonymous polymorphisms, are increasingly studied for their functional impact.
  • While the link between silent mutations, tRNA abundance, and protein folding is established in prokaryotes, it remains debated in eukaryotes.
  • Previous work demonstrated that the estrogen receptor alpha Ala87 synonymous polymorphism affects protein function.

Purpose of the Study:

  • To investigate the role of isoacceptor tRNA frequencies in eukaryotic protein folding.
  • To explore how changes in the tRNA pool, influenced by cellular states, affect protein conformation and function.

Main Methods:

  • Analysis of synonymous polymorphism effects on protein properties.
  • Review of literature on tRNA abundance, posttranscriptional modifications, and their relation to cellular states (proliferation, stress).
  • Exploration of the impact of translation kinetics modulation by tRNA frequencies on protein folding.

Main Results:

  • Synonymous polymorphisms can alter mRNA structure or ligand interactions.
  • Isoacceptor tRNA frequencies may significantly influence protein folding by modulating translation kinetics.
  • Cellular state changes correlate with significant alterations in the tRNA pool, including quantitative and qualitative modifications.
  • These tRNA pool dynamics can lead to protein conformational variants with diverse functional consequences.

Conclusions:

  • The genetic code's flexibility, particularly tRNA pool dynamics, plays a crucial role in co-translational protein folding in eukaryotes.
  • Changes in tRNA populations during different cellular states can lead to functionally relevant protein conformational variations.
  • Further research into the interplay between silent mutations, tRNA biology, and protein folding is warranted.