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Related Concept Videos

Improving Translational Accuracy02:07

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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 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
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ER is the primary site for the maturation and folding of soluble and transmembrane secretory proteins. The calnexin cycle is a specific chaperone system that folds and assesses the confirmation of N-glycosylated proteins before they can exit the ER lumen. The primary players of this quality check pipeline are the lectins, ER-resident chaperones, and a glucosyl transferase enzyme. In case the calnexin system in the lumen fails to salvage a misfolded protein, it is transported to the cytoplasm...
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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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The organelle-specific signaling sequences direct proteins synthesized in the cytosol to their final destination like ER, mitochondria, peroxisomes, etc. Some of the proteins directed to ER are then trafficked via vesicles to other organelles within the cell or the extracellular environment through the Golgi complex. For example, the rough ER synthesizes soluble proteins for transportation to the lysosomes or secretion out of the cell. It can also synthesize transmembrane proteins that can...
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Related Experiment Video

Updated: Oct 29, 2025

Global Identification of Co-Translational Interaction Networks by Selective Ribosome Profiling
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Ribosome-associated quality control and CAT tailing.

Conor J Howard1, Adam Frost1

  • 1Department of Biochemistry and Biophysics, University of California, San Francisco, CA, USA.

Critical Reviews in Biochemistry and Molecular Biology
|July 8, 2021
PubMed
Summary

Life depends on ribosome-associated quality control (RQC) to manage translation errors and prevent toxic protein buildup. Recent research highlights RQC

Keywords:
CAT tailsLUCARQCRibosome-associated quality controlorigins of lifepeptide synthesisprotein translationproteostasis

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Genome-wide Quantification of Translation in Budding Yeast by Ribosome Profiling
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Area of Science:

  • Molecular Biology
  • Genetics
  • Biochemistry

Background:

  • Ribosomes are essential for protein synthesis but prone to errors, leading to stalled translation.
  • Stalled translation can result from various factors including aberrant mRNAs, mRNA structures, defective ribosomes, and limited cellular resources like tRNA.
  • Quality control mechanisms are crucial for detecting, disassembling, and recycling stalled translation intermediates to maintain cellular function.

Purpose of the Study:

  • To review recent advances in understanding Ribosome-associated Quality Control (RQC) across different organisms.
  • To focus on the Carboxy-terminal Alanine and Threonine (CAT) tail modification and its synthesis mechanisms.
  • To explore the role of ancient RQC proteins in managing aberrant translation.

Main Methods:

  • Literature review of recent research on RQC mechanisms.
  • Analysis of studies investigating nascent polypeptide modifications.
  • Comparative examination of RQC pathways in bacteria, fungi, and metazoans.

Main Results:

  • RQC pathways are conserved across bacteria, fungi, and metazoans.
  • A key RQC mechanism involves the synthesis of a Carboxy-terminal Alanine and Threonine (CAT) tail on nascent polypeptides.
  • Ancient RQC proteins are responsible for catalyzing CAT-tail synthesis, targeting potentially toxic polypeptides for degradation.

Conclusions:

  • RQC is a vital cellular process for mitigating the consequences of translation errors.
  • The CAT tail modification is a significant feature of RQC, ensuring the proper handling of aberrant translation products.
  • Understanding RQC mechanisms provides insights into protein homeostasis and disease prevention.