ArticleNucleic acids research2007
The tetraplex (CGG)n destabilizing proteins hnRNP A2 and CBF-A enhance the in vivo translation of fragile X premutation mRNA.
Article in Nucleic acids research, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 87 citations in OpenAlex.
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- Structural Unfolding of G-Quadruplexes: From Small Molecules to Antisense Strategies.Molecules (Basel, Switzerland) · 2024Review
- RNA structure promotes liquid-to-solid phase transition of short RNAs in neuronal dysfunction.Communications biology · 2024Article
- RNA G-quadruplex organizes stress granule assembly through DNAPTP6 in neurons.Science advances · 2023Article
- G-quadruplexes and associated proteins in aging and Alzheimer's disease.Frontiers in aging · 2023Review
- High-throughput characterization of the role of non-B DNA motifs on promoter function.Cell genomics · 2022Article
- Non-canonical DNA/RNA structures associated with the pathogenesis of Fragile X-associated tremor/ataxia syndrome and Fragile X syndrome.Frontiers in genetics · 2022Review
- (Dys)function Follows Form: Nucleic Acid Structure, Repeat Expansion, and Disease Pathology inInternational journal of molecular sciences · 2021Review
- A Minimalistic Coumarin Turn-On Probe for Selective Recognition of Parallel G-Quadruplex DNA Structures.ACS chemical biology · 2021Article
- RNA G-quadruplexes (rG4s): genomics and biological functions.Nucleic acids research · 2021Review
- Enhanced detection of expanded repeat mRNA foci with hybridization chain reaction.Acta neuropathologica communications · 2021Article
- Secondary structural choice of DNA and RNA associated with CGG/CCG trinucleotide repeat expansion rationalizes the RNA misprocessing in FXTAS.Scientific reports · 2021Article
- The Cellular Functions and Molecular Mechanisms of G-Quadruplex Unwinding Helicases in Humans.Frontiers in molecular biosciences · 2021Review
- G-quadruplexes Stabilization Upregulates CCN1 and Accelerates Aging in Cultured Cerebral Endothelial Cells.Frontiers in aging · 2021Article
- The regulation and functions of DNA and RNA G-quadruplexes.Nature reviews. Molecular cell biology · 2020Review
- G-Quadruplexes in Human Ribosomal RNA.Journal of molecular biology · 2019Article
- Targeted Reactivation ofFrontiers in molecular neuroscience · 2018Article
- Comprehensive identification of proteins binding to RNA G-quadruplex motifs in the 5' UTR of tumor-associated mRNAs.Biochimie · 2018Article
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Authors and funding
5 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Expansion of a (CGG)n sequence in the 5'-UTR of the FMR1 gene to >200-2000 repeats abolishes its transcription and initiates fragile X syndrome (FXS). By contrast, levels of FMR1 mRNA are 5-10-fold higher in FXS premutation carriers of >55-200 repeats than in normal subjects. Lack of a corresponding increase in the amount of the product FMRP protein in carrier cells suggest that (CGG)>55-200 tracts thwart translation. Here we report that a (CGG)99 sequence positioned upstream to reporter firefly (FL) gene selectively diminished mRNA translation in coupled and separate T7 promoter-driven in vitro transcription and translation systems. The (CGG)99 tract similarly depressed mRNA utilization in HEK293 human cells transfected with plasmids bearing FMR1 promoter-driven FL gene. A (CGG)33 RNA tract formed a largely RNase T1-resistant intramolecular secondary structure in the presence of K+ ions. Expression of the quadruplex (CGG)n disrupting proteins hnRNP A2 or CBF-A in HEK293 cells significantly elevated the efficacy of (CGG)99 FL mRNA translation whereas hnRNP A2 or CBF-A mutants lacking quadruplex (CGG)n disrupting activity did not. Taken together, our results suggest that secondary structures of (CGG)n in mRNA obstruct its translation and that quadruplex-disrupting proteins alleviate the translational block.
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