JBC GenomeOne product landing page

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Originally published In Press as doi:10.1074/jbc.M105113200 on September 17, 2001

J. Biol. Chem., Vol. 276, Issue 46, 42986-42993, November 16, 2001
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
276/46/42986    most recent
M105113200v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kalbfuss, B.
Right arrow Articles by Misteli, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kalbfuss, B.
Right arrow Articles by Misteli, T.

Correction of Alternative Splicing of Tau in Frontotemporal Dementia and Parkinsonism Linked to Chromosome 17*

Bernd Kalbfuss, Stephen A. Mabon, and Tom MisteliDagger

From National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892

Mutations in the human tau gene cause frontotemporal dementia and Parkinsonism associated with chromosome 17 (FTDP-17). One of the major disease mechanisms in FTDP-17 is the increased inclusion of tau exon 10 during pre-mRNA splicing. Here we show that modified oligonucleotides directed against the tau exon 10 splice junctions suppress inclusion of tau exon 10. The effect is mediated by the formation of a stable pre-mRNA-oligonucleotide hybrid, which blocks access of the splicing machinery to the pre-mRNA. Correction of tau splicing occurs in a tau minigene system and in endogenous tau RNA in neuronal pheochromocytoma cells and is specific to exon 10 of the tau gene. Antisense oligonucleotide-mediated exclusion of exon 10 has a physiological effect by increasing the ratio of protein lacking the microtubule-binding domain encoded by exon 10. As a consequence, the microtubule cytoskeleton becomes destabilized and cell morphology is altered. Our results demonstrate that alternative splicing defects of tau as found in FTDP-17 patients can be corrected by application of antisense oligonucleotides. These findings provide a tool to study specific tau isoforms in vivo and might lead to a novel therapeutic strategy for FTDP-17.

* The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Dagger To whom correspondence should be addressed: NCI, National Institutes of Health, 41 Library Dr., Bldg. 41, Bethesda, MD 20892. Tel.: 301-402-3959; Fax: 520-832-0970; E-mail: mistelit@mail.nih.gov.

Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.


This article has been cited by other articles:


Home page
 RNAHome page
A. Aartsma-Rus and G.-J. B. van Ommen
Antisense-mediated exon skipping: A versatile tool with therapeutic and research applications
RNA, October 1, 2007; 13(10): 1609 - 1624.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
C. P. Donahue, C. Muratore, J. Y. Wu, K. S. Kosik, and M. S. Wolfe
Stabilization of the Tau Exon 10 Stem Loop Alters Pre-mRNA Splicing
J. Biol. Chem., August 18, 2006; 281(33): 23302 - 23306.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
J.-M. Gallo, P. Jin, C. A. Thornton, H. Lin, J. Robertson, I. D'Souza, and W. W. Schlaepfer
The Role of RNA and RNA Processing in Neurodegeneration
J. Neurosci., November 9, 2005; 25(45): 10372 - 10375.
[Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
T. Rodriguez-Martin, M. A. Garcia-Blanco, S. G. Mansfield, A. C. Grover, M. Hutton, Q. Yu, J. Zhou, B. H. Anderton, and J.-M. Gallo
Reprogramming of tau alternative splicing by spliceosome-mediated RNA trans-splicing: Implications for tauopathies
PNAS, October 25, 2005; 102(43): 15659 - 15664.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
M. Gabut, M. Mine, C. Marsac, M. Brivet, J. Tazi, and J. Soret
The SR Protein SC35 Is Responsible for Aberrant Splicing of the E1{alpha} Pyruvate Dehydrogenase mRNA in a Case of Mental Retardation with Lactic Acidosis
Mol. Cell. Biol., April 15, 2005; 25(8): 3286 - 3294.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
P. Fehlbaum, C. Guihal, L. Bracco, and O. Cochet
A microarray configuration to quantify expression levels and relative abundance of splice variants
Nucleic Acids Res., March 10, 2005; 33(5): e47 - e47.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
D. Ittig, S. Liu, D. Renneberg, D. Schumperli, and C. J. Leumann
Nuclear antisense effects in cyclophilin A pre-mRNA splicing by oligonucleotides: a comparison of tricyclo-DNA with LNA
Nucleic Acids Res., January 15, 2004; 32(1): 346 - 353.
[Abstract] [Full Text] [PDF]

Home page
 Genes Dev.Home page
N. A. Faustino and T. A. Cooper
Pre-mRNA splicing and human disease
Genes & Dev., February 15, 2003; 17(4): 419 - 437.
[Full Text] [PDF]

Home page
 BloodHome page
M. M. Vacek, H. Ma, F. Gemignani, G. Lacerra, T. Kafri, and R. Kole
High-level expression of hemoglobin A in human thalassemic erythroid progenitor cells following lentiviral vector delivery of an antisense snRNA
Blood, January 1, 2003; 101(1): 104 - 111.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 All ASBMB Journals   Molecular and Cellular Proteomics 
 Journal of Lipid Research   ASBMB Today 
Copyright © 2001 by the American Society for Biochemistry and Molecular Biology.