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Food-Derived Compounds Apigenin and Luteolin Modulate mRNA Splicing of Introns with Weak Splice Sites

288 Pages Posted: 22 Aug 2019 Sneak Peek Status: Review Complete

See all articles by Masashi Kurata

Masashi Kurata

Kyoto University - Division of Integrated Life Sciences

Naoko Fujiwara

Kyoto University - Division of Integrated Life Sciences

Ken-ichi Fujita

Kyoto University - Division of Integrated Life Sciences

Yasutaka Yamanaka

Kyoto University - Division of Integrated Life Sciences

Shigeto Seno

Osaka University - Department of Bioinformatic Engineering

Hisato Kobayashi

Tokyo University of Agriculture - NODAI Genome Research Center

Nobuyuki Takahashi

Tokyo University of Agriculture - Department of Nutritional Science and Food Safety

Yasuyuki Shibuya

Nagoya City University

Seiji Masuda

Kyoto University

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Abstract

Cancer cells often exhibit an extreme sensitivity to splicing inhibitors. We identified food-derived flavonoids, apigenin and luteolin, as compounds that modulate mRNA splicing at the genome-wide level followed by proliferation inhibition. They bind to mRNA splicing-related proteins to induce widespread change of splicing patterns in treated cells. Their inhibitory activity on splicing is relatively moderate, and introns with weak splice sites tend to be sensitive to them. Such introns remain unspliced, and the resulting intron-containing mRNAs are retained in the nucleus, resulting in the nuclear accumulation of bulk poly(A)+ RNAs in these flavonoid-treated cells. Tumorigenic cells are more susceptible to these flavonoids than non-tumorigenic cells, both for the nuclear poly(A)+ RNA-accumulating phenotype and cell viability. This study illustrates the possible mechanism of these flavonoids to suppress tumor progression in vivo demonstrated in previous studies and provides the potential of daily intake of moderate splicing inhibitors to prevent cancer development.

Suggested Citation

Kurata, Masashi and Fujiwara, Naoko and Fujita, Ken-ichi and Yamanaka, Yasutaka and Seno, Shigeto and Kobayashi, Hisato and Takahashi, Nobuyuki and Shibuya, Yasuyuki and Masuda, Seiji, Food-Derived Compounds Apigenin and Luteolin Modulate mRNA Splicing of Introns with Weak Splice Sites (August 21, 2019). ISCIENCE-D-19-00782. Available at SSRN: https://ssrn.com/abstract=3440259 or http://dx.doi.org/10.2139/ssrn.3440259
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Masashi Kurata

Kyoto University - Division of Integrated Life Sciences ( email )

Kyoto
Japan

Naoko Fujiwara

Kyoto University - Division of Integrated Life Sciences ( email )

Kyoto
Japan

Ken-ichi Fujita

Kyoto University - Division of Integrated Life Sciences ( email )

Kyoto
Japan

Yasutaka Yamanaka

Kyoto University - Division of Integrated Life Sciences ( email )

Kyoto
Japan

Shigeto Seno

Osaka University - Department of Bioinformatic Engineering ( email )

Osaka
Japan

Hisato Kobayashi

Tokyo University of Agriculture - NODAI Genome Research Center ( email )

Tokyo
Japan

Nobuyuki Takahashi

Tokyo University of Agriculture - Department of Nutritional Science and Food Safety ( email )

Tokyo
Japan

Yasuyuki Shibuya

Nagoya City University

1 Kawasumi
Mizuho-cho, Mizuho-ku
Nagoya, 467-8601
Japan

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