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Related Concept Videos

Improving Translational Accuracy02:07

Improving Translational Accuracy

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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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Ribosome synthesis is a highly complex and coordinated process involving more than 200 assembly factors. The synthesis and processing of ribosomal components occurs not only in the nucleolus but also in the nucleoplasm and the cytoplasm of eukaryotic cells.
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Bacterial protein maturation is a tightly regulated process that ensures newly synthesized polypeptides achieve correct functional conformations. This maturation involves a series of modifications, folding events, and quality control steps, often assisted by specialized chaperone proteins.N-Terminal ModificationsThe maturation of bacterial polypeptides begins cotranslationally as the polypeptide exits the ribosome. The first amino acid, N-formylmethionine (fMet), is typically modified at the...
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Termination of Translation01:44

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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...
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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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Related Experiment Video

Updated: Sep 29, 2025

Eukaryotic Polyribosome Profile Analysis
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eIF6 rebinding dynamically couples ribosome maturation and translation.

Pekka Jaako1,2,3,4, Alexandre Faille1,2,3, Shengjiang Tan1,2,3

  • 1Cambridge Institute for Medical Research, Cambridge Biomedical Campus, Keith Peters Building, Hills Rd, Cambridge, CB2 0XY, UK.

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|March 24, 2022
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Summary
This summary is machine-generated.

SBDS and EFL1 release the anti-association factor eIF6, enabling 60S ribosomal subunit recycling for protein synthesis. Disrupting this process impairs erythropoiesis and is linked to Shwachman-Diamond syndrome.

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Area of Science:

  • Molecular Biology
  • Cell Biology
  • Genetics

Background:

  • Protein synthesis is a fundamental cellular process involving translation initiation, elongation, termination, and ribosome recycling.
  • The anti-association factor eIF6 maintains free cytoplasmic 60S ribosomal subunits in an inactive state.
  • Mutations in SBDS and EFL1 are associated with Shwachman-Diamond syndrome, a leukemia predisposition disorder.

Purpose of the Study:

  • To elucidate the role of SBDS and EFL1 in ribosome recycling and protein synthesis.
  • To investigate the mechanism by which eIF6 regulates 60S ribosomal subunit activity.
  • To understand how disruptions in ribosome recycling contribute to Shwachman-Diamond syndrome.

Main Methods:

  • Investigated the function of SBDS and EFL1 in mammalian cell cultures.
  • Assessed the impact of eIF6 levels on erythropoiesis in vivo using mouse models.
  • Analyzed the regulation of 60S ribosomal subunit association and protein synthesis.

Main Results:

  • SBDS and EFL1 are essential for evicting eIF6 from the 60S ribosomal subunit, thereby licensing it for translation.
  • eIF6 sequesters post-termination 60S subunits, inhibiting ribosome joining and global protein synthesis.
  • Elevated eIF6 levels in mice impair terminal erythropoiesis.

Conclusions:

  • Ribosome maturation and recycling are dynamically coupled processes regulated by the interplay between eIF6, SBDS, and EFL1.
  • Dysregulation of this ribosome recycling mechanism is implicated in Shwachman-Diamond syndrome.
  • Targeting this pathway may offer therapeutic strategies for related disorders.