Gene expression, 2005-01, Vol.12 (3), p.213-222
2005
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Details
- Autor(en) / Beteiligte
- Titel
- Allele-Specific Conditional Destabilization of Glutamine Repeat mRNAs
- Ist Teil von
- Gene expression, 2005-01, Vol.12 (3), p.213-222
- Ort / Verlag
- Elmsford, NY: Cognizant Communication Corporation
- Erscheinungsjahr
- 2005
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Several late-onset neurological diseases are caused by the inheritance of an expanded CAG repeat coding for polyglutamine. To date there is no effective means of halting the progression of these diseases, and their underlying molecular mechanisms remain a mystery. Strategies designed to specifically reduce the levels of long repeat mRNA might provide an effective therapy for these diseases. An emphasis on allele specificity is necessary to avoid the potential toxicities associated with reduction of expression. The experiments described here are based on the relationship between translation and mRNA stability and the idea that translation of a repeated codon might be extremely sensitive to reductions in levels of cognate aminoacylated tRNA. Consistent with this hypothesis, we have discovered that reduced glutamine concentration destabilizes mRNAs coding for long glutamine repeats while sparing short repeat versions of the same mRNAs. These results suggest therapy might be attained with existing compounds or environmental conditions known to decrease free glutamine levels.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1052-2166eISSN: 1555-3884DOI: 10.3727/000000005783992089Titel-ID: cdi_ingenta_journals_cog_ge_2005_00000012_00000003_art00006
- Format
- –
- Schlagworte
- Alleles, Animals, Base Sequence, Brain, Codon, Design, Destabilization, Disease, Dose-Response Relationship, Drug, Embryo, Mammalian - cytology, Environmental conditions, Gene expression, Gene Expression Regulation, Genome, Human, Glutamine, Glutamine - chemistry, Glutamine - metabolism, Glutamine - pharmacology, Humans, Huntington Disease - genetics, Huntington Disease - metabolism, Huntington's Disease, Mice, Models, Genetic, Models, Theoretical, Molecular modelling, Molecular Sequence Data, Mrna Stability, Neurological diseases, Neurological disorders, Patients, Peptides - chemistry, Peptides - metabolism, Polyglutamine, Protein Biosynthesis, Proteins, Rational Therapeutic, Reverse Transcriptase Polymerase Chain Reaction, Ribonucleic acid, RNA, RNA, Messenger - metabolism, RNA, Transfer - metabolism, Stem Cells - cytology, Time Factors, Transfer RNA, Translation, Trinucleotide repeat diseases, Trinucleotide Repeat Expansion, Trinucleotide Repeats, Trna