Regulation of alternative splicing of tau exon 10 by 9G8 and Dyrk1A
Abstract Adult human brain expresses 6 isoforms of tau protein as a result of alternative splicing. Alternative splicing of exon 10 (E10) leads to tau isoforms containing either 3 (3R-tau) or 4 (4R-tau) microtubule-binding repeats. Imbalance in the 3R-tau/4R-tau ratio causes neurofibrillary degenera...
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Published in | Neurobiology of aging Vol. 33; no. 7; pp. 1389 - 1399 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Elsevier Inc
01.07.2012
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Subjects | |
Online Access | Get full text |
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Summary: | Abstract Adult human brain expresses 6 isoforms of tau protein as a result of alternative splicing. Alternative splicing of exon 10 (E10) leads to tau isoforms containing either 3 (3R-tau) or 4 (4R-tau) microtubule-binding repeats. Imbalance in the 3R-tau/4R-tau ratio causes neurofibrillary degeneration and dementia. Here, we demonstrated that the dual-specificity tyrosine phosphorylation-regulated kinase 1A (Dyrk1A) interacted with the splicing factor 9G8 and phosphorylated it at several serine residues. Dyrk1A itself promoted tau E10 inclusion, whereas 9G8 inhibited E10 inclusion, and these actions were variable depending on the cell types. Coexpression of Dyrk1A and 9G8 led to their translocation from the nucleus to the cytoplasm and suppressed their ability to regulate tau exon 10 splicing. This action is probably due to their interaction-induced translocation from the nucleus, where the regulation of tau E10 splicing occurs, to the cytoplasm. These findings provide novel insights into the molecular mechanism of the regulation of tau E10 splicing and further our understanding of the neurodegeneration caused by dysregulation of tau E10 splicing. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Article-2 ObjectType-Feature-1 These authors contribute to this study equally. |
ISSN: | 0197-4580 1558-1497 |
DOI: | 10.1016/j.neurobiolaging.2010.11.021 |