Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Experiment Videos

Dimerization of a pathogenic human mitochondrial tRNA.

Lisa M Wittenhagen1, Shana O Kelley

  • 1Department of Chemistry, Boston College, Chestnut Hill, Massachusetts 02467, USA.

Nature Structural Biology
|July 9, 2002
PubMed
Summary

The common A3243G mitochondrial mutation causes transfer RNA (tRNA) to form dimers, disrupting its structure and function. This tRNA dimerization leads to multisystemic diseases due to reduced biological activity.

Related Concept Videos

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

AI-guided CRISPR screening reveals therapeutic targets in psoriasis.

Nature communications·2026
Same author

Integrating Transcription Factors with Electrochemical Pendulum Bioanalysis for Hormone Detection.

Journal of the American Chemical Society·2026
Same author

Biomolecular Condensates as Protein Degradation Tools for Intracellular Targets.

Nature communications·2026
Same author

Resilient nanostructured bioanalytic microneedle longitudinally monitors preclinical renal and hepatic drug clearance and dysfunction.

Science translational medicine·2026
Same author

Amino acid supplementation enhances in vivo efficacy of lipid nanoparticle-mediated mRNA delivery in preclinical models.

Science translational medicine·2026
Same author

Toward Reagentless and Universal Biomolecular Sensing: Molecular Pendulum-Based Bioanalysis.

Accounts of chemical research·2025

Area of Science:

  • Molecular Biology
  • Genetics
  • Biochemistry

Background:

  • Mitochondrial mutations, particularly in transfer RNA (tRNA), are linked to various multisystemic diseases.
  • The A3243G substitution in the mitochondrial tRNA(Leu(UUR)) gene is the most frequent pathogenic mutation.

Purpose of the Study:

  • To elucidate the structural consequences of the A3243G mutation in human mitochondrial tRNA(Leu(UUR)).
  • To investigate the impact of these structural changes on tRNA function and disease pathogenesis.

Main Methods:

  • Structural analysis of the mutant tRNA.
  • Biochemical assays to assess aminoacylation levels.
  • Mutational studies to identify functional domains.

Main Results:

  • The A3243G mutation induces significant tRNA dimerization under physiological conditions.
  • Dimerization occurs via a hexanucleotide interface in the D-stem of tRNA(Leu(UUR)).
  • Aminoacylation of the mutant tRNA is substantially reduced, with dimerization contributing to this loss of function.

Conclusions:

  • The pathogenic A3243G mutation destabilizes native tRNA structure, promoting dimerization and reduced biological activity.
  • Disruption of a conserved tertiary structural contact further impairs tRNA function.
  • These molecular defects provide a mechanism for the multisystemic diseases associated with this common mitochondrial mutation.

Related Experiment Videos