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Related Concept Videos

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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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.
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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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Related Experiment Video

Updated: Jan 9, 2026

Quantitative Immunofluorescence to Measure Global Localized Translation
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GCN2 monitors mRNA translation termination.

Kailey Worner1, Katharine R Maschhoff1, Gabrielle M Schuh1

  • 1Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905, USA.

Molecular Cell
|December 10, 2025
PubMed
Summary
This summary is machine-generated.

Impaired translation termination rapidly activates GCN2, leading to eIF2α phosphorylation and blocked translation initiation. This conserved surveillance mechanism prevents ribosome collisions and translation errors.

Keywords:
GCN2dTAGeIF2α phosphorylationeRF1terminating ribosometranslation termination

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Area of Science:

  • Molecular Biology
  • Cellular Biology
  • Genetics

Background:

  • Regulation of mRNA translation is crucial for protein synthesis.
  • Mechanisms monitoring translation termination are poorly understood.
  • Translation initiation and elongation are well-studied regulatory steps.

Purpose of the Study:

  • To investigate the cellular response to impaired translation termination.
  • To identify surveillance mechanisms that monitor translation termination.
  • To understand how translation termination defects impact cellular processes.

Main Methods:

  • Utilized an acute protein degradation system.
  • Employed phenotypic rescue via ectopic expression.
  • Performed ribosome profiling analyses.

Main Results:

  • Impaired translation termination rapidly activates GCN2 kinase.
  • Activated GCN2 phosphorylates eIF2α, inhibiting translation initiation.
  • GCN2 monitors terminating ribosomes, preventing collisions and readthrough.
  • This response is conserved across stem/somatic cells and mouse/human cells.

Conclusions:

  • A conserved surveillance mechanism monitors translation termination.
  • GCN2 plays a key role in detecting and responding to translation termination defects.
  • This mechanism prevents potentially harmful cellular consequences of faulty translation termination.