Journal of Alzheimer's Disease
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Home > SIRT1 Deacetylates SC35 and Suppresses Its Function in Tau Exon 10 Inclusion.

TitleSIRT1 Deacetylates SC35 and Suppresses Its Function in Tau Exon 10 Inclusion.
Publication TypeJournal Article
Year of Publication2018
AuthorsYin, X, Jiang, X, Wang, J, Qian, S, Liu, F, Qian, W
JournalJ Alzheimers Dis
Volume61
Issue2
Pagination561-570
Date Published2018
ISSN1875-8908
KeywordsAlternative Splicing, Alzheimer Disease, Exons, HEK293 Cells, HeLa Cells, Humans, Phosphorylation, Ribonucleoproteins, Serine-Arginine Splicing Factors, Sirtuin 1, tau Proteins, Tauopathies
Abstract

Approximately equal amounts of 3R-tau and 4R-tau resulting from alternative splicing of tau exon 10 is necessary to maintain normal brain function. Dysregulation of alternative splicing of tau exon 10 and the imbalance of 3R-tau/4R-tau have been seen in inherited and sporadic tauopathies. Splicing factor SC35 (also name as SRSF2) plays an important role in promoting tau exon 10 inclusion. SC35 is post-translationally modified by phosphorylation and acetylation, but the role of acetylation in SC35-medicated tau exon 10 inclusion is unknown. Sirtuin type 1 (SIRT1) is an enzyme that deacetylates proteins and associates with age-related disease such as Alzheimer's disease. In the present study, we determined the role of SIRT1 in SC35 acetylation and in the alternative splicing of tau exon 10. We found that SIRT1 interacts with and deacetylates SC35, and inhibits SC35-promoted tau exon 10 inclusion. Substituting K52 residue of SC35 by arginine impairs the role of SC35 in tau exon 10 inclusion. These results suggest that SIRT1 may serve as a therapeutic target for tauopathy by regulating SC35-mediated tau exon 10 splicing.

DOI10.3233/JAD-170418
Alternate JournalJ. Alzheimers Dis.
PubMed ID29226865
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Source URL: https://www.j-alz.com/content/sirt1-deacetylates-sc35-and-suppresses-its-function-tau-exon-10-inclusion