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Transcript errors generate amyloid-like proteins in human cells
by
Moore, Darcie L.
, Li, Zhongwei
, Carrillo, Lucy
, Thomas, Kelley W.
, Quadrato, Giorgia
, Jin, Yuxin
, Vermulst, Marc
, Rosenthal, Joshua J. C.
, Sun, Yingwo
, Verheijen, Bert M.
, Shemtov, Sarah J.
, Del Dosso, Ashley
, Hicks, Daniel
, Jauregui, Ashley Michelle
, Kennedy, Scott R.
, Flores, Ilse
, Biao, Huang
, Toney, Renaldo G.
, Gout, Jean-Francois
, Chen, Lin
, Benayoun, Bérénice A.
, Love, Kayla
, Chung, Claire S.
, Simpson, Stephen
, Thorwald, Max A.
, Liu, Yuchen
, Quiroz, Juan Diaz
, Nguyen, Megan M.
, Kou, Yi
, Coba, Marcelo P.
, Head, Elizabeth
in
14
/ 14/19
/ 14/28
/ 38
/ 38/109
/ 38/91
/ 631/337/572
/ 631/45/470/2284
/ 631/80/304
/ 82/83
/ Age related diseases
/ Aging
/ Alzheimer's disease
/ Amyotrophic lateral sclerosis
/ Brain damage
/ Cell differentiation
/ Disease
/ DNA damage
/ Errors
/ Genomes
/ Humanities and Social Sciences
/ Hypotheses
/ Molecular modelling
/ mRNA
/ multidisciplinary
/ Mutants
/ Mutation
/ Neurogenesis
/ Organoids
/ Pathology
/ Proteins
/ Science
/ Science (multidisciplinary)
/ Stem cells
2024
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Transcript errors generate amyloid-like proteins in human cells
by
Moore, Darcie L.
, Li, Zhongwei
, Carrillo, Lucy
, Thomas, Kelley W.
, Quadrato, Giorgia
, Jin, Yuxin
, Vermulst, Marc
, Rosenthal, Joshua J. C.
, Sun, Yingwo
, Verheijen, Bert M.
, Shemtov, Sarah J.
, Del Dosso, Ashley
, Hicks, Daniel
, Jauregui, Ashley Michelle
, Kennedy, Scott R.
, Flores, Ilse
, Biao, Huang
, Toney, Renaldo G.
, Gout, Jean-Francois
, Chen, Lin
, Benayoun, Bérénice A.
, Love, Kayla
, Chung, Claire S.
, Simpson, Stephen
, Thorwald, Max A.
, Liu, Yuchen
, Quiroz, Juan Diaz
, Nguyen, Megan M.
, Kou, Yi
, Coba, Marcelo P.
, Head, Elizabeth
in
14
/ 14/19
/ 14/28
/ 38
/ 38/109
/ 38/91
/ 631/337/572
/ 631/45/470/2284
/ 631/80/304
/ 82/83
/ Age related diseases
/ Aging
/ Alzheimer's disease
/ Amyotrophic lateral sclerosis
/ Brain damage
/ Cell differentiation
/ Disease
/ DNA damage
/ Errors
/ Genomes
/ Humanities and Social Sciences
/ Hypotheses
/ Molecular modelling
/ mRNA
/ multidisciplinary
/ Mutants
/ Mutation
/ Neurogenesis
/ Organoids
/ Pathology
/ Proteins
/ Science
/ Science (multidisciplinary)
/ Stem cells
2024
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Transcript errors generate amyloid-like proteins in human cells
by
Moore, Darcie L.
, Li, Zhongwei
, Carrillo, Lucy
, Thomas, Kelley W.
, Quadrato, Giorgia
, Jin, Yuxin
, Vermulst, Marc
, Rosenthal, Joshua J. C.
, Sun, Yingwo
, Verheijen, Bert M.
, Shemtov, Sarah J.
, Del Dosso, Ashley
, Hicks, Daniel
, Jauregui, Ashley Michelle
, Kennedy, Scott R.
, Flores, Ilse
, Biao, Huang
, Toney, Renaldo G.
, Gout, Jean-Francois
, Chen, Lin
, Benayoun, Bérénice A.
, Love, Kayla
, Chung, Claire S.
, Simpson, Stephen
, Thorwald, Max A.
, Liu, Yuchen
, Quiroz, Juan Diaz
, Nguyen, Megan M.
, Kou, Yi
, Coba, Marcelo P.
, Head, Elizabeth
in
14
/ 14/19
/ 14/28
/ 38
/ 38/109
/ 38/91
/ 631/337/572
/ 631/45/470/2284
/ 631/80/304
/ 82/83
/ Age related diseases
/ Aging
/ Alzheimer's disease
/ Amyotrophic lateral sclerosis
/ Brain damage
/ Cell differentiation
/ Disease
/ DNA damage
/ Errors
/ Genomes
/ Humanities and Social Sciences
/ Hypotheses
/ Molecular modelling
/ mRNA
/ multidisciplinary
/ Mutants
/ Mutation
/ Neurogenesis
/ Organoids
/ Pathology
/ Proteins
/ Science
/ Science (multidisciplinary)
/ Stem cells
2024
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Transcript errors generate amyloid-like proteins in human cells
Journal Article
Transcript errors generate amyloid-like proteins in human cells
2024
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Overview
Aging is characterized by the accumulation of proteins that display amyloid-like behavior. However, the molecular mechanisms by which these proteins arise remain unclear. Here, we demonstrate that amyloid-like proteins are produced in a variety of human cell types, including stem cells, brain organoids and fully differentiated neurons by mistakes that occur in messenger RNA molecules. Some of these mistakes generate mutant proteins already known to cause disease, while others generate proteins that have not been observed before. Moreover, we show that these mistakes increase when cells are exposed to DNA damage, a major hallmark of human aging. When taken together, these experiments suggest a mechanistic link between the normal aging process and age-related diseases.
Amyloid-like proteins are central to age-related diseases, such as Alzheimer’s and Parkinson’s. Here, the authors show that transcription errors can produce mutant proteins with enhanced amyloid- and prion-like properties in human cells.
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