Transcript errors generate amyloid-like proteins in human cells
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.
Authors
- Joshua J. C. Rosenthal (ORCID: https://orcid.org/0000-0001-8139-9364)
- Marc Vermulst (ORCID: https://orcid.org/0000-0003-4909-5496)
- Jean-François Goût (ORCID: https://orcid.org/0000-0002-4549-5647)
- Darcie L. Moore (ORCID: https://orcid.org/0000-0002-0854-7655)
- Scott R. Kennedy (ORCID: https://orcid.org/0000-0002-4444-1145)
- Ilse Flores
- Ashley Michelle Jauregui
- Bérénice Anath Benayoun (ORCID: https://orcid.org/0000-0002-7401-4777)
- Yi Kou (ORCID: https://orcid.org/0000-0002-7139-2043)
- Marcelo P. Coba (ORCID: https://orcid.org/0000-0001-7075-6338)
- Yuxin Jin (ORCID: https://orcid.org/0000-0002-6124-9681)
- Max A. Thorwald
- Giorgia Quadrato (ORCID: https://orcid.org/0000-0003-0717-4874)
- Elizabeth Head (ORCID: https://orcid.org/0000-0003-1115-6396)
- Kayla Love
- Megan Nguyen
- Bert M. Verheijen (ORCID: https://orcid.org/0000-0002-1818-443X)
- Ashley Del Dosso
- Sarah J. Shemtov (ORCID: https://orcid.org/0000-0002-8176-1105)
- W. Kelley Thomas (ORCID: https://orcid.org/0000-0002-0945-5269)
- Renaldo G. Toney (ORCID: https://orcid.org/0009-0007-0335-7004)
- Yuchen Liu (ORCID: https://orcid.org/0000-0002-6517-0022)
- Lin Chen (ORCID: https://orcid.org/0000-0003-4798-6199)
- Zhongwei Li (ORCID: https://orcid.org/0000-0002-5997-5422)
- Yingwo Sun
- Stephen Simpson (ORCID: https://orcid.org/0000-0002-4383-3972)
- Biao Huang (ORCID: https://orcid.org/0000-0003-2948-665X)
- Claire S. Chung (ORCID: https://orcid.org/0009-0002-5024-3871)
- Juan Diaz Quiroz
- Lucy Carrillo
- Daniel Hicks
Institutions
- University of Southern California (US)
- Marine Biological Laboratory (US)
- University of Wisconsin–Madison (US)
- University of New Hampshire (US)
- University of Washington (US)
- University of California, Irvine (US)
- Broad Center (US)
- Seattle University (US)
- Mississippi State University (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-10-07
- DOI
- https://doi.org/10.1038/s41467-024-52886-2
- Citations
- 11
- Primary Topic
- CRISPR and Genetic Engineering
- Type
- article
- Field-Weighted Citation Impact
- 2.57
Funders
- National Institutes of Health
- University of California, Irvine
- National Institute on Aging