Modulation of the membrane-binding projection domain of tau protein: Splicing regulation of exon 3

Meltem Cevik Arikan; John Memmott; Jennifer A. Broderick; Athena Andreadis; Athena Andreadis; Robert Lafyatis; Gavin Screaton; Stefan Stamm

doi:10.1016/S0169-328X(02)00178-X

Modulation of the membrane-binding projection domain of tau protein: Splicing regulation of exon 3

Meltem Cevik Arikan, John Memmott, Jennifer A. Broderick, Athena Andreadis, Athena Andreadis, Robert Lafyatis, Gavin Screaton, Stefan Stamm

Research output: Contribution to journal › Article › peer-review

21 Scopus citations

Abstract

Tau is a microtubule-associated protein whose transcript undergoes complex regulated splicing in the mammalian nervous system. The N-terminal domain of the protein interacts with the axonal membrane, and is modulated by differential inclusion of exons 2 and 3. These two tau exons are alternatively spliced cassettes, in which exon 3 never appears independently of exon 2. Previous work with tau minigene constructs indicated that exon 3 is intrinsically suboptimal and its primary regulator is a weak branch point. In this study, we confirm the role of the weak branch point in the regulation of exon 3 but also show that the exon is additionally regulated by a combination of exonic enhancers and silencers. Furthermore, we demonstrate that known splicing regulators affect the ratio of exon 3 isoforms, Lastly, we tentatively pinpoint the site of action of several splicing factors which regulate tau exon 3.

Original language	English
Pages (from-to)	109-121
Number of pages	13
Journal	Molecular Brain Research
Volume	101
Issue number	1-2
DOIs	https://doi.org/10.1016/S0169-328X(02)00178-X
State	Published - May 30 2002

Bibliographical note

Funding Information:
This work was supported by NIH RO1 grant NS38051 (A.A.), an Arthritis Foundation Medical Science Grant (R.L.), Deutsche Forschungsgemeinschaft SFB 473 (S.S.), and the Medical Research Council (G.S.). We want to thank our colleagues for their generous gifts of factor cDNAs: Drs. Joanne Yeakley and Javier Cáceres for ASF, James Patton for PTB, Benoit Chabot for hnRNPA1 and Christopher Smith for SV-αTM.

Keywords

Alternative splicing
MAP tau
Membrane-interacting domain
Regulated isoform
cis and trans splicing regulator

ASJC Scopus subject areas

Molecular Biology
Cellular and Molecular Neuroscience

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10.1016/S0169-328X(02)00178-X

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title = "Modulation of the membrane-binding projection domain of tau protein: Splicing regulation of exon 3",

abstract = "Tau is a microtubule-associated protein whose transcript undergoes complex regulated splicing in the mammalian nervous system. The N-terminal domain of the protein interacts with the axonal membrane, and is modulated by differential inclusion of exons 2 and 3. These two tau exons are alternatively spliced cassettes, in which exon 3 never appears independently of exon 2. Previous work with tau minigene constructs indicated that exon 3 is intrinsically suboptimal and its primary regulator is a weak branch point. In this study, we confirm the role of the weak branch point in the regulation of exon 3 but also show that the exon is additionally regulated by a combination of exonic enhancers and silencers. Furthermore, we demonstrate that known splicing regulators affect the ratio of exon 3 isoforms, Lastly, we tentatively pinpoint the site of action of several splicing factors which regulate tau exon 3.",

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author = "Arikan, {Meltem Cevik} and John Memmott and Broderick, {Jennifer A.} and Athena Andreadis and Athena Andreadis and Robert Lafyatis and Gavin Screaton and Stefan Stamm",

note = "Funding Information: This work was supported by NIH RO1 grant NS38051 (A.A.), an Arthritis Foundation Medical Science Grant (R.L.), Deutsche Forschungsgemeinschaft SFB 473 (S.S.), and the Medical Research Council (G.S.). We want to thank our colleagues for their generous gifts of factor cDNAs: Drs. Joanne Yeakley and Javier C{\'a}ceres for ASF, James Patton for PTB, Benoit Chabot for hnRNPA1 and Christopher Smith for SV-αTM.",

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AU - Arikan, Meltem Cevik

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AU - Broderick, Jennifer A.

AU - Andreadis, Athena

AU - Lafyatis, Robert

AU - Screaton, Gavin

AU - Stamm, Stefan

N1 - Funding Information: This work was supported by NIH RO1 grant NS38051 (A.A.), an Arthritis Foundation Medical Science Grant (R.L.), Deutsche Forschungsgemeinschaft SFB 473 (S.S.), and the Medical Research Council (G.S.). We want to thank our colleagues for their generous gifts of factor cDNAs: Drs. Joanne Yeakley and Javier Cáceres for ASF, James Patton for PTB, Benoit Chabot for hnRNPA1 and Christopher Smith for SV-αTM.

PY - 2002/5/30

Y1 - 2002/5/30

N2 - Tau is a microtubule-associated protein whose transcript undergoes complex regulated splicing in the mammalian nervous system. The N-terminal domain of the protein interacts with the axonal membrane, and is modulated by differential inclusion of exons 2 and 3. These two tau exons are alternatively spliced cassettes, in which exon 3 never appears independently of exon 2. Previous work with tau minigene constructs indicated that exon 3 is intrinsically suboptimal and its primary regulator is a weak branch point. In this study, we confirm the role of the weak branch point in the regulation of exon 3 but also show that the exon is additionally regulated by a combination of exonic enhancers and silencers. Furthermore, we demonstrate that known splicing regulators affect the ratio of exon 3 isoforms, Lastly, we tentatively pinpoint the site of action of several splicing factors which regulate tau exon 3.

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Modulation of the membrane-binding projection domain of tau protein: Splicing regulation of exon 3

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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