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Related Concept Videos

Nonsense-mediated mRNA Decay02:27

Nonsense-mediated mRNA Decay

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The Upf proteins that carry out nonsense-mediated decay (NMD) are found in all eukaryotic organisms, including humans. Each protein has an individual role, but they need to work in collaboration. Upf1 is an ATP-dependent RNA helicase that unwinds the RNA helix. Because Upf1 can unwind any RNA, Upf2 and Upf3 are required to help Upf1 discriminate between nonsense and normal mRNAs.
Usually, Upf3 binds to an Exon Junction Complex (EJC) at mRNA splice sites. If a ribosome fully translates the mRNA,...
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Leaky Scanning02:28

Leaky Scanning

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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...
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Transcription Attenuation in Prokaryotes02:42

Transcription Attenuation in Prokaryotes

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Transcriptional attenuation occurs when RNA transcription is prematurely terminated due to the formation of a terminator mRNA hairpin structure.  Bacteria use these hairpins to regulate the transcription process and control the synthesis of several amino acids including histidine, lysine, threonine, and phenylalanine. Transcription attenuation takes place in the non-coding regions of mRNA.
There are several different mechanisms used to attenuate transcription. In ribosome mediated...
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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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Nuclear Export of mRNA02:31

Nuclear Export of mRNA

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Before mRNAs are exported to the cytoplasm, it is crucial to check each mRNA for structural and functional integrity. Eukaryotic cells use several different mechanisms, collectively known as mRNA surveillance, to look for irregularities in mRNAs. Irregular or aberrant mRNA are rapidly degraded by various enzymes. If a defective mRNA escapes the surveillance, it would be translated into a protein which would either be non-functional or not function properly. One of the primary irregularities in...
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Termination of Translation01:44

Termination of Translation

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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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Updated: Jul 25, 2025

Analysis of Termination of Transcription Using BrUTP-strand-specific Transcription Run-on TRO Approach
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Analysis of Termination of Transcription Using BrUTP-strand-specific Transcription Run-on TRO Approach

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Pharmaceuticals Promoting Premature Termination Codon Readthrough: Progress in Development.

Shan Li1, Juan Li2,3, Wenjing Shi1

  • 1School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China.

Biomolecules
|June 28, 2023
PubMed
Summary

Nonsense mutations cause genetic diseases, but drugs called translational readthrough-inducing drugs (TRIDs) can help. This review covers TRIDs, offering hope for treating these conditions.

Keywords:
nonsense mutationnonsense suppressionpremature termination codon (PTC)readthrough therapytranslational readthrough-inducing drugs (TRIDs)

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High-throughput Screening for Chemical Modulators of Post-transcriptionally Regulated Genes
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Last Updated: Jul 25, 2025

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Area of Science:

  • Genetics
  • Pharmacology
  • Molecular Biology

Background:

  • Nonsense mutations, responsible for 11% of genetic diseases, introduce premature stop codons (PTCs).
  • Drug-induced PTC readthrough is a therapeutic strategy for genetic disorders caused by nonsense mutations.

Purpose of the Study:

  • To review the pharmacodynamics and clinical potential of translational readthrough-inducing drugs (TRIDs).
  • To highlight newly discovered TRIDs and their implications for treating genetic diseases.

Main Methods:

  • Literature review of small-molecular compounds promoting PTC readthrough.
  • Categorization of TRIDs into aminoglycosides and non-aminoglycosides.
  • Summary of pharmacodynamics and clinical application potential.

Main Results:

  • Over 50 small-molecular compounds (TRIDs) identified, promoting PTC readthrough.
  • TRIDs are broadly classified into aminoglycosides and non-aminoglycosides.
  • Recent discoveries offer new therapeutic avenues for genetic diseases.

Conclusions:

  • TRIDs offer significant hope for treating genetic diseases caused by nonsense mutations.
  • Further research into eukaryotic termination and TRID mechanisms is crucial for patient benefit.