Splicing factor ASF/SF2 and transcription factor PPAR-γ cooperate to directly regulate transcription of uncoupling protein-3

Dong Joon Kim; Bermseok Oh; Young Youl Kim

doi:10.1016/j.bbrc.2008.12.009

Splicing factor ASF/SF2 and transcription factor PPAR-γ cooperate to directly regulate transcription of uncoupling protein-3

Dong Joon Kim, Bermseok Oh, Young Youl Kim

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

14 Citations (Scopus)

Abstract

The different isoforms of the uncoupling protein-3 (UCP3) are expressed in skeletal muscle and are up-regulated by splicing factors. Here, we report that UCP3 alternative splicing (alternative polyadenylation) is regulated by cooperation between the splicing factor ASF/SF2 and the transcription factor PPAR-γ. We found that ASF/SF2 activates formation of long-form UCP3 (UCP3_L) by inhibiting a cleavage and polyadenylation signal (AATAAA) located in its final intron that prematurely terminates message elongation. PPAR-γ activates this process by directly interacting with ASF/SF2, providing the first example of a direct link between a transcription factor and alternative splicing. Activation of ASF/SF2 promotes formation of UCP3_L, whereas loss of ASF/SF2 decreases production of both UCP3_L and short-form UCP3 (UCP3_S). We suggest that the relative abundance of ASF/SF2 and PPAR-γ determines the ratio of UCP3 isoforms.

Original language	English
Pages (from-to)	877-882
Number of pages	6
Journal	Biochemical and Biophysical Research Communications
Volume	378
Issue number	4
DOIs	https://doi.org/10.1016/j.bbrc.2008.12.009
Publication status	Published - 23 Jan 2009

Bibliographical note

Funding Information:
This study was supported by a grant from the Korean National Institute of the Health Intramural Fund (Serial Number: 2007-N00339-00 and 2008-N00395-00).

Keywords

Alternative splicing
Skeletal muscle
Uncoupling protein-3

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title = "Splicing factor ASF/SF2 and transcription factor PPAR-γ cooperate to directly regulate transcription of uncoupling protein-3",

abstract = "The different isoforms of the uncoupling protein-3 (UCP3) are expressed in skeletal muscle and are up-regulated by splicing factors. Here, we report that UCP3 alternative splicing (alternative polyadenylation) is regulated by cooperation between the splicing factor ASF/SF2 and the transcription factor PPAR-γ. We found that ASF/SF2 activates formation of long-form UCP3 (UCP3L) by inhibiting a cleavage and polyadenylation signal (AATAAA) located in its final intron that prematurely terminates message elongation. PPAR-γ activates this process by directly interacting with ASF/SF2, providing the first example of a direct link between a transcription factor and alternative splicing. Activation of ASF/SF2 promotes formation of UCP3L, whereas loss of ASF/SF2 decreases production of both UCP3L and short-form UCP3 (UCP3S). We suggest that the relative abundance of ASF/SF2 and PPAR-γ determines the ratio of UCP3 isoforms.",

keywords = "Alternative splicing, Skeletal muscle, Uncoupling protein-3",

author = "Kim, {Dong Joon} and Bermseok Oh and Kim, {Young Youl}",

note = "Funding Information: This study was supported by a grant from the Korean National Institute of the Health Intramural Fund (Serial Number: 2007-N00339-00 and 2008-N00395-00).",

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AU - Oh, Bermseok

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N1 - Funding Information: This study was supported by a grant from the Korean National Institute of the Health Intramural Fund (Serial Number: 2007-N00339-00 and 2008-N00395-00).

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N2 - The different isoforms of the uncoupling protein-3 (UCP3) are expressed in skeletal muscle and are up-regulated by splicing factors. Here, we report that UCP3 alternative splicing (alternative polyadenylation) is regulated by cooperation between the splicing factor ASF/SF2 and the transcription factor PPAR-γ. We found that ASF/SF2 activates formation of long-form UCP3 (UCP3L) by inhibiting a cleavage and polyadenylation signal (AATAAA) located in its final intron that prematurely terminates message elongation. PPAR-γ activates this process by directly interacting with ASF/SF2, providing the first example of a direct link between a transcription factor and alternative splicing. Activation of ASF/SF2 promotes formation of UCP3L, whereas loss of ASF/SF2 decreases production of both UCP3L and short-form UCP3 (UCP3S). We suggest that the relative abundance of ASF/SF2 and PPAR-γ determines the ratio of UCP3 isoforms.

AB - The different isoforms of the uncoupling protein-3 (UCP3) are expressed in skeletal muscle and are up-regulated by splicing factors. Here, we report that UCP3 alternative splicing (alternative polyadenylation) is regulated by cooperation between the splicing factor ASF/SF2 and the transcription factor PPAR-γ. We found that ASF/SF2 activates formation of long-form UCP3 (UCP3L) by inhibiting a cleavage and polyadenylation signal (AATAAA) located in its final intron that prematurely terminates message elongation. PPAR-γ activates this process by directly interacting with ASF/SF2, providing the first example of a direct link between a transcription factor and alternative splicing. Activation of ASF/SF2 promotes formation of UCP3L, whereas loss of ASF/SF2 decreases production of both UCP3L and short-form UCP3 (UCP3S). We suggest that the relative abundance of ASF/SF2 and PPAR-γ determines the ratio of UCP3 isoforms.

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KW - Skeletal muscle

KW - Uncoupling protein-3

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ER -

Splicing factor ASF/SF2 and transcription factor PPAR-γ cooperate to directly regulate transcription of uncoupling protein-3

Abstract

Bibliographical note

Keywords

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