ArticleThe Journal of biological chemistry2011
Translational repression of the disintegrin and metalloprotease ADAM10 by a stable G-quadruplex secondary structure in its 5'-untranslated region.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 86 citations in OpenAlex.
- RNA G-quadruplexes promote codon repeat-associated ribosomal frameshifting in human genes.Nucleic acids research · 2026Article
- RNA G-Quadruplex RIBOTAC-Mediated Targeted Degradation of lncRNA TERRA.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Evolutionary dynamics of predicted G-quadruplexes in human and other great apes.Genome biology · 2025Article
- Structural Features of 5' Untranslated Region in Translational Control of Eukaryotes.International journal of molecular sciences · 2025Review
- 5'-UTR G-Quadruplex-Mediated Translation Regulation in Eukaryotes: Current Understanding and Methodological Challenges.International journal of molecular sciences · 2025Review
- A Valuable Target for Therapy: The Metalloproteinase ADAM10.Current protein & peptide science · 2025Review
- Selective recognition of RNA G-quadruplex in vitro and in cells by L-aptamer-D-oligonucleotide conjugate.Nucleic acids research · 2024Article
- SHMT2 Mediates Small-Molecule-Induced Alleviation of Alzheimer Pathology Via the 5'UTR-dependent ADAM10 Translation Initiation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- G-quadruplex formation in RNA aptamers selected for binding to HIV-1 capsid.Frontiers in chemistry · 2024Article
- A Bioengineering Strategy to Control ADAM10 Activity in Living Cells.International journal of molecular sciences · 2023Article
- Toward a Better Understanding of G4 Evolution in the 3 Living Kingdoms.Evolutionary bioinformatics online · 2023Article
- G-quadruplexes and associated proteins in aging and Alzheimer's disease.Frontiers in aging · 2023Review
- Gaining Insights on the Interactions of a Class of Decorated (2-([2,2'-Bipyridin]-6-yl)phenyl)platinum Compounds with c-Myc Oncogene Promoter G-Quadruplex and Other DNA Structures.Chemistry (Weinheim an der Bergstrasse, Germany) · 2022Article
- Reversal of G-Quadruplexes' Role in Translation Control When Present in the Context of an IRES.Biomolecules · 2022Review
- Secondary structures in RNA synthesis, splicing and translation.Computational and structural biotechnology journal · 2022Review
- G-Quadruplexes in Neurobiology and Virology: Functional Roles and Potential Therapeutic Approaches.JACS Au · 2021Review
- RNA G-quadruplex structures control ribosomal protein production.Scientific reports · 2021Article
- Redox-Active Metal Ions and Amyloid-Degrading Enzymes in Alzheimer's Disease.International journal of molecular sciences · 2021Review
- RNA G-quadruplexes (rG4s): genomics and biological functions.Nucleic acids research · 2021Review
- G-Quadruplexes as pathogenic drivers in neurodegenerative disorders.Nucleic acids research · 2021Review
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Authors and funding
8 authors at 2 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
Anti-amyloidogenic processing of the amyloid precursor protein APP by α-secretase prevents formation of the amyloid-β peptide, which accumulates in senile plaques of Alzheimer disease patients. α-Secretase belongs to the family of a disintegrin and metalloproteases (ADAMs), and ADAM10 is the primary candidate for this anti-amyloidogenic activity. We recently demonstrated that ADAM10 translation is repressed by its 5'-UTR and that in particular the first half of ADAM10 5'-UTR is responsible for translational repression. Here, we asked whether specific sequence motifs exist in the ADAM10 5'-UTR that are able to form complex secondary structures and thus potentially inhibit ADAM10 translation. Using circular dichroism spectroscopy, we demonstrate that a G-rich region between nucleotides 66 and 94 of the ADAM10 5'-UTR forms a highly stable, intramolecular, parallel G-quadruplex secondary structure under physiological conditions. Mutation of guanines in this sequence abrogates the formation of the G-quadruplex structure. Although the G-quadruplex structure efficiently inhibits translation of a luciferase reporter in in vitro translation assays and in living cells, inhibition of G-quadruplex formation fails to do so. Moreover, expression of ADAM10 was similarly repressed by the G-quadruplex. Mutation of the G-quadruplex motif results in a significant increase of ADAM10 levels and consequently APPsα secretion. Thus, we identified a critical RNA secondary structure within the 5'-UTR, which contributes to the translational repression of ADAM10.
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