Alternative splicing produces a constitutively active form of human SREBP-1

Nagakatsu Harada; Haruka Yonemoto; Masaki Yoshida; Hironori Yamamoto; Yunjie Yin; Aiko Miyamoto; Atsushi Hattori; Qishisan Wu; Tadahiko Nakagawa; Masayuki Nakano; Kiyoshi Teshigawara; Kazuaki Mawatari; Toshio Hosaka; Akira Takahashi; Yutaka Nakaya

doi:10.1016/j.bbrc.2008.02.004

Alternative splicing produces a constitutively active form of human SREBP-1

Nagakatsu Harada, Haruka Yonemoto, Masaki Yoshida, Hironori Yamamoto, Yunjie Yin, Aiko Miyamoto, Atsushi Hattori, Qishisan Wu, Tadahiko Nakagawa, Masayuki Nakano, Kiyoshi Teshigawara, Kazuaki Mawatari, Toshio Hosaka, Akira Takahashi, Yutaka Nakaya

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

17 Citations (Scopus)

Abstract

We identified a novel alternative splicing event that constitutively produces a truncated active form of human sterol regulatory element-binding protein 1 (SREBP-1). A cDNA of this splicing variant (named SREBP-1Δ) contains a translational stop codon-encoding exon sequence between exons 7 and 8. It produces SREBP-1aΔ (470 a.a.) and SREBP-1cΔ (446 a.a.) proteins that lack transmembrane and C-terminal regulatory sequences necessary for localization of SREBP-1 to the endoplasmic reticulum. A luciferase reporter assay showed that SREBP-1aΔ and SREBP-1cΔ transactivated lipogenic gene promoters to the same extent as that induced by N-terminal active fragments of SREBP-1a and SREBP-1c, respectively. SREBP-1Δ mRNA is expressed in human cell lines as well as adipose and liver tissues. Expression levels ranged from 5% to 16% of total SREBP-1 expression. The ratio of SREBP-1Δ expression to total SREBP-1 expression in HepG2 cells was not affected by either insulin or high glucose treatment.

Original language	English
Pages (from-to)	820-826
Number of pages	7
Journal	Biochemical and Biophysical Research Communications
Volume	368
Issue number	3
DOIs	https://doi.org/10.1016/j.bbrc.2008.02.004
Publication status	Published - Apr 11 2008
Externally published	Yes

Keywords

Alternative splicing
High glucose
Insulin
Promoter activity
Sterol regulatory element-binding protein

ASJC Scopus subject areas

Biophysics
Biochemistry
Molecular Biology
Cell Biology

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10.1016/j.bbrc.2008.02.004

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Harada, N., Yonemoto, H., Yoshida, M., Yamamoto, H., Yin, Y., Miyamoto, A., Hattori, A., Wu, Q., Nakagawa, T., Nakano, M., Teshigawara, K., Mawatari, K., Hosaka, T., Takahashi, A., & Nakaya, Y. (2008). Alternative splicing produces a constitutively active form of human SREBP-1. Biochemical and Biophysical Research Communications, 368(3), 820-826. https://doi.org/10.1016/j.bbrc.2008.02.004

Harada, N, Yonemoto, H, Yoshida, M, Yamamoto, H, Yin, Y, Miyamoto, A, Hattori, A, Wu, Q, Nakagawa, T, Nakano, M, Teshigawara, K, Mawatari, K, Hosaka, T, Takahashi, A & Nakaya, Y 2008, 'Alternative splicing produces a constitutively active form of human SREBP-1', Biochemical and Biophysical Research Communications, vol. 368, no. 3, pp. 820-826. https://doi.org/10.1016/j.bbrc.2008.02.004

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abstract = "We identified a novel alternative splicing event that constitutively produces a truncated active form of human sterol regulatory element-binding protein 1 (SREBP-1). A cDNA of this splicing variant (named SREBP-1Δ) contains a translational stop codon-encoding exon sequence between exons 7 and 8. It produces SREBP-1aΔ (470 a.a.) and SREBP-1cΔ (446 a.a.) proteins that lack transmembrane and C-terminal regulatory sequences necessary for localization of SREBP-1 to the endoplasmic reticulum. A luciferase reporter assay showed that SREBP-1aΔ and SREBP-1cΔ transactivated lipogenic gene promoters to the same extent as that induced by N-terminal active fragments of SREBP-1a and SREBP-1c, respectively. SREBP-1Δ mRNA is expressed in human cell lines as well as adipose and liver tissues. Expression levels ranged from 5% to 16% of total SREBP-1 expression. The ratio of SREBP-1Δ expression to total SREBP-1 expression in HepG2 cells was not affected by either insulin or high glucose treatment.",

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T1 - Alternative splicing produces a constitutively active form of human SREBP-1

AU - Harada, Nagakatsu

AU - Yonemoto, Haruka

AU - Yoshida, Masaki

AU - Yamamoto, Hironori

AU - Yin, Yunjie

AU - Miyamoto, Aiko

AU - Hattori, Atsushi

AU - Wu, Qishisan

AU - Nakagawa, Tadahiko

AU - Nakano, Masayuki

AU - Teshigawara, Kiyoshi

AU - Mawatari, Kazuaki

AU - Hosaka, Toshio

AU - Takahashi, Akira

AU - Nakaya, Yutaka

PY - 2008/4/11

Y1 - 2008/4/11

N2 - We identified a novel alternative splicing event that constitutively produces a truncated active form of human sterol regulatory element-binding protein 1 (SREBP-1). A cDNA of this splicing variant (named SREBP-1Δ) contains a translational stop codon-encoding exon sequence between exons 7 and 8. It produces SREBP-1aΔ (470 a.a.) and SREBP-1cΔ (446 a.a.) proteins that lack transmembrane and C-terminal regulatory sequences necessary for localization of SREBP-1 to the endoplasmic reticulum. A luciferase reporter assay showed that SREBP-1aΔ and SREBP-1cΔ transactivated lipogenic gene promoters to the same extent as that induced by N-terminal active fragments of SREBP-1a and SREBP-1c, respectively. SREBP-1Δ mRNA is expressed in human cell lines as well as adipose and liver tissues. Expression levels ranged from 5% to 16% of total SREBP-1 expression. The ratio of SREBP-1Δ expression to total SREBP-1 expression in HepG2 cells was not affected by either insulin or high glucose treatment.

AB - We identified a novel alternative splicing event that constitutively produces a truncated active form of human sterol regulatory element-binding protein 1 (SREBP-1). A cDNA of this splicing variant (named SREBP-1Δ) contains a translational stop codon-encoding exon sequence between exons 7 and 8. It produces SREBP-1aΔ (470 a.a.) and SREBP-1cΔ (446 a.a.) proteins that lack transmembrane and C-terminal regulatory sequences necessary for localization of SREBP-1 to the endoplasmic reticulum. A luciferase reporter assay showed that SREBP-1aΔ and SREBP-1cΔ transactivated lipogenic gene promoters to the same extent as that induced by N-terminal active fragments of SREBP-1a and SREBP-1c, respectively. SREBP-1Δ mRNA is expressed in human cell lines as well as adipose and liver tissues. Expression levels ranged from 5% to 16% of total SREBP-1 expression. The ratio of SREBP-1Δ expression to total SREBP-1 expression in HepG2 cells was not affected by either insulin or high glucose treatment.

KW - Alternative splicing

KW - High glucose

KW - Insulin

KW - Promoter activity

KW - Sterol regulatory element-binding protein

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Alternative splicing produces a constitutively active form of human SREBP-1

Abstract

Keywords

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