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All fields Title Creator / Publisher Keyword Year AND OR AND NOT All fields Title Creator / Publisher Keyword Year AND OR AND NOT All fields Title Creator / Publisher Keyword Year AND OR AND NOT All fields Title Creator / Publisher Keyword Year AND OR AND NOT All fields Title Creator / Publisher Keyword Year Sort by creator [A → Z]' creator [Z → A]' publishing year ↑ (asc)' publishing year ↓ (desc)' title [A → Z]' title [Z → A]' Simple Search Hits 1 – 8 of 8 1 Repeat-Associated Non-Aug Translation Initiation at Expanded Ggggcc Repeats in c9orf72-Associated Amyotrophic Lateral Sclerosis and Frontotemporal Dementia Green, Katelyn. - 2020 BASE Show details 2 DDX3X and specific initiation factors modulate FMR1 repeat‐associated non‐AUG‐initiated translation Linsalata, Alexander E; He, Fang; Malik, Ahmed M; Glineburg, Mary Rebecca; Green, Katelyn M; Natla, Sam; Flores, Brittany N; Krans, Amy; Archbold, Hilary C; Fedak, Stephen J; Barmada, Sami J; Todd, Peter K. - : Wiley Periodicals, Inc., 2019 Abstract: A CGG trinucleotide repeat expansion in the 5′ UTR of FMR1 causes the neurodegenerative disorder Fragile X‐associated tremor/ataxia syndrome (FXTAS). This repeat supports a non‐canonical mode of protein synthesis known as repeat‐associated, non‐AUG (RAN) translation. The mechanism underlying RAN translation at CGG repeats remains unclear. To identify modifiers of RAN translation and potential therapeutic targets, we performed a candidate‐based screen of eukaryotic initiation factors and RNA helicases in cell‐based assays and a Drosophila melanogaster model of FXTAS. We identified multiple modifiers of toxicity and RAN translation from an expanded CGG repeat in the context of the FMR1 5′UTR. These include the DEAD‐box RNA helicase belle/DDX3X, the helicase accessory factors EIF4B/4H, and the start codon selectivity factors EIF1 and EIF5. Disrupting belle/DDX3X selectively inhibited FMR1 RAN translation in Drosophila in vivo and cultured human cells, and mitigated repeat‐induced toxicity in Drosophila and primary rodent neurons. These findings implicate RNA secondary structure and start codon fidelity as critical elements mediating FMR1 RAN translation and identify potential targets for treating repeat‐associated neurodegeneration.SynopsisFragile X‐associated tremor/ataxia syndrome is caused by CGG repeat‐associated non‐AUG (RAN) translation that initiates within the 5′UTR of FMR1. A candidate‐based screen identified several initiation factors—DDX3X/Belle, eIF4B, eIF4H, eIF1, and eIF5—critical for FMR1 RAN translation.Knockdown of the RNA helicase DDX3X selectively suppresses FMR1 RAN translation in Drosophila melanogaster, cultured HeLa cells, and in vitro translation assays.DDX3X knockdown reduces CGG repeat‐associated toxicity in Drosophila and mammalian neurons.Eukaryotic initiation factors that modulate RNA‐RNA secondary structure (DDX3X, EIF4B, EIF4H) or start codon fidelity (EIF1, EIF5) impact FMR1 RAN translation.FXTAS is caused by CGG repeat‐associated non‐AUG (RAN) translation that initiates within the 5′UTR of FMR1. A candidate‐based screen identified several initiation factors—DDX3X/Belle, eIF4B, eIF4H, eIF1, and eIF5—critical for FMR1 RAN translation. ; Peer Reviewed ; https://deepblue.lib.umich.edu/bitstream/2027.42/151325/1/embr201847498.reviewer_comments.pdf ; https://deepblue.lib.umich.edu/bitstream/2027.42/151325/2/embr201847498-sup-0001-Appendix.pdf ; https://deepblue.lib.umich.edu/bitstream/2027.42/151325/3/embr201847498_am.pdf ; https://deepblue.lib.umich.edu/bitstream/2027.42/151325/4/embr201847498.pdf Keyword: Cellular and Developmental Biology; DDX3X; eIF; Fragile X‐associated tremor/ataxia syndrome; Health Sciences; Molecular; RAN translation; RNA helicase URL: https://doi.org/10.15252/embr.201847498 https://hdl.handle.net/2027.42/151325 BASE Hide details 3 High-throughput screening yields several small-molecule inhibitors of repeat-associated non-AUG translation Green, Katelyn M.; Sheth, Udit J.; Flores, Brittany N.... In: J Biol Chem (2019) BASE Show details 4 Ribosome queuing enables non-AUG translation to be resistant to multiple protein synthesis inhibitors Kearse, Michael G.; Goldman, Daniel H.; Choi, Jiou. - : Cold Spring Harbor Laboratory Press, 2019 BASE Show details 5 DDX3X and specific initiation factors modulate FMR1 repeat‐associated non‐AUG‐initiated translation Linsalata, Alexander E; He, Fang; Malik, Ahmed M... In: EMBO Rep (2019) BASE Show details 6 RAN translation at C9orf72-associated repeat expansions is selectively enhanced by the integrated stress response Green, Katelyn M.; Glineburg, M. Rebecca; Kearse, Michael G.. - : Nature Publishing Group UK, 2017 BASE Show details 7 CGG Repeat associated non-AUG translation utilizes a cap-dependent, scanning mechanism of initiation to produce toxic proteins Kearse, Michael G.; Green, Katelyn M.; Krans, Amy. - 2016 BASE Show details 8 RAN translation—what makes it run? Green, Katelyn M.; Linsalata, Alexander E.; Todd, Peter K.. - 2016 BASE Show details

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