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• W4313366945 abstract "Extended CAG trinucleotide repeats (TNR) in the genes huntingtin (HTT) and androgen receptor (AR) are the cause of two progressive neurodegenerative disorders: Huntington's disease (HD) and Spinal and Bulbar Muscular Atrophy (SBMA), respectively. Anyone who inherits the mutant gene in the complete penetrance range (>39 repeats for HD and 44 for SBMA) will develop the disease. An inverse correlation exists between the length of the CAG repeat and the severity and age of onset of the diseases. Growing evidence suggests that it is the length of uninterrupted CAG repeats in the mRNA rather than the length of poly glutamine (polyQ) in mutant (m)HTT protein that determines disease progression. One variant of mHTT (loss of inhibition; LOI) causes a 25 year earlier onset of HD when compared to a reference sequence, despite both coding for a protein that contains an identical number of glutamines. Short 21-22 nt CAG repeat (sCAGs)-containing RNAs can cause disease through RNA interference (RNAi). RNA hairpins (HPs) forming at the CAG TNRs are stabilized by adjacent CCG (in HD) or CUG repeats (in SBMA) making them better substrates for Dicer, the enzyme that processes CAG HPs into sCAGs. We now show that cells deficient in Dicer or unable to mediate RNAi are resistant to the toxicity of the HTT and AR derived HPs. Expression of a small HP that mimics the HD LOI variant is more stable and more toxic than a reference HP. We report that the LOI HP is processed by Dicer, loaded into the RISC more efficiently, and gives rise to a higher quantity of RISC-bound 22 nt sCAGs. Our data support the notion that RNAi contributes to the cell death seen in HD and SBMA and provide an explanation for the dramatically reduced onset of disease in HD patients that carry the LOI variant." @default.
• W4313366945 created "2023-01-06" @default.
• W4313366945 creator A5019985517 @default.
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• W4313366945 creator A5071711769 @default.
• W4313366945 date "2022-12-30" @default.
• W4313366945 modified "2023-10-09" @default.
• W4313366945 title "The length of uninterrupted CAG repeats in stem regions of repeat disease associated hairpins determines the amount of short CAG oligonucleotides that are toxic to cells through RNA interference" @default.
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• W4313366945 cites W2037288833 @default.
• W4313366945 cites W2040271470 @default.
• W4313366945 cites W2052883021 @default.
• W4313366945 cites W2054109341 @default.
• W4313366945 cites W2054166086 @default.
• W4313366945 cites W2054982708 @default.
• W4313366945 cites W2064551580 @default.
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• W4313366945 cites W2073012734 @default.
• W4313366945 cites W2081280332 @default.
• W4313366945 cites W2081635886 @default.
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• W4313366945 doi "https://doi.org/10.1038/s41419-022-05494-1" @default.
• W4313366945 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36585400" @default.
• W4313366945 hasPublicationYear "2022" @default.
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• W4313366945 hasAuthorship W4313366945A5071711769 @default.

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