Nature Communications (Oct 2024)
Transcript errors generate amyloid-like proteins in human cells
- Claire S. Chung,
- Yi Kou,
- Sarah J. Shemtov,
- Bert M. Verheijen,
- Ilse Flores,
- Kayla Love,
- Ashley Del Dosso,
- Max A. Thorwald,
- Yuchen Liu,
- Daniel Hicks,
- Yingwo Sun,
- Renaldo G. Toney,
- Lucy Carrillo,
- Megan M. Nguyen,
- Huang Biao,
- Yuxin Jin,
- Ashley Michelle Jauregui,
- Juan Diaz Quiroz,
- Elizabeth Head,
- Darcie L. Moore,
- Stephen Simpson,
- Kelley W. Thomas,
- Marcelo P. Coba,
- Zhongwei Li,
- Bérénice A. Benayoun,
- Joshua J. C. Rosenthal,
- Scott R. Kennedy,
- Giorgia Quadrato,
- Jean-Francois Gout,
- Lin Chen,
- Marc Vermulst
Affiliations
- Claire S. Chung
- University of Southern California, Leonard Davis School of Gerontology
- Yi Kou
- University of Southern California, Molecular and Cellular Biology Department
- Sarah J. Shemtov
- University of Southern California, Leonard Davis School of Gerontology
- Bert M. Verheijen
- University of Southern California, Leonard Davis School of Gerontology
- Ilse Flores
- University of Southern California, Keck School of Medicine
- Kayla Love
- University of Southern California, Molecular and Cellular Biology Department
- Ashley Del Dosso
- University of Southern California, Eli and Edythe Broad CIRM Center for Regenerative Medicine and Stem Cell Research
- Max A. Thorwald
- University of Southern California, Leonard Davis School of Gerontology
- Yuchen Liu
- University of Southern California, Molecular and Cellular Biology Department
- Daniel Hicks
- University of Southern California, Leonard Davis School of Gerontology
- Yingwo Sun
- University of Southern California, Leonard Davis School of Gerontology
- Renaldo G. Toney
- University of Southern California, Leonard Davis School of Gerontology
- Lucy Carrillo
- University of Southern California, Leonard Davis School of Gerontology
- Megan M. Nguyen
- University of Washington, Department of Pathology and Laboratory Medicine
- Huang Biao
- University of Southern California, Eli and Edythe Broad CIRM Center for Regenerative Medicine and Stem Cell Research
- Yuxin Jin
- University of Southern California, Keck School of Medicine
- Ashley Michelle Jauregui
- University of Southern California, Keck School of Medicine
- Juan Diaz Quiroz
- Marine Biological Laboratory, Bell Center
- Elizabeth Head
- University of California Irvine, Department of Pathology and Laboratory Medicine
- Darcie L. Moore
- University of Wisconsin, Department of Neuroscience
- Stephen Simpson
- University of New Hampshire, Department of Molecular, Cellular, & Biomedical Sciences
- Kelley W. Thomas
- University of New Hampshire, Department of Molecular, Cellular, & Biomedical Sciences
- Marcelo P. Coba
- University of Southern California, Keck School of Medicine
- Zhongwei Li
- University of Southern California, Eli and Edythe Broad CIRM Center for Regenerative Medicine and Stem Cell Research
- Bérénice A. Benayoun
- University of Southern California, Leonard Davis School of Gerontology
- Joshua J. C. Rosenthal
- Marine Biological Laboratory, Bell Center
- Scott R. Kennedy
- University of Washington, Department of Pathology and Laboratory Medicine
- Giorgia Quadrato
- University of Southern California, Eli and Edythe Broad CIRM Center for Regenerative Medicine and Stem Cell Research
- Jean-Francois Gout
- Mississippi State University, Department of Biology
- Lin Chen
- University of Southern California, Molecular and Cellular Biology Department
- Marc Vermulst
- University of Southern California, Leonard Davis School of Gerontology
- DOI
- https://doi.org/10.1038/s41467-024-52886-2
- Journal volume & issue
-
Vol. 15,
no. 1
pp. 1 – 17
Abstract
Abstract 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.
