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Updated: Jun 27, 2026

Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells
Published on: April 26, 2017
Splicing factor ASF/SF2 and transcription factor PPAR-gamma cooperate to directly regulate transcription of
Dong-Joon Kim1, Bermseok Oh, Young-Youl Kim
1Center for Genome Science, National Institute of Health in Korea, Eunpyung-Gu, Seoul, Republic of Korea.
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-gamma. 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-gamma 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-gamma determines the ratio of UCP3 isoforms.
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