Establishment of a Monitoring System to Detect Inhibition of mRNA Processing

Fujita, Ken‐ichi; Okamura, Masumi; Nishimoto, Sei‐ichi; Kurihara, Tomoya; Momma, Keiko; Miyamae, Yusaku; Kambe, Taiho; Nagao, Masaya; Narita, Hiroshi; Masuda, Seiji

doi:10.1271/bbb.120226

Cited by 8 publications

(15 citation statements)

References 11 publications

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“…The inhibitory activity of mRNA from dietary origin was examined by the previously established monitoring system to assess the inhibition of mRNA processing including Renilla luciferase assay and RNA-FISH [35,39]. The addition of soybean flavone fraction, Soya flavone HG (SHG) (Fuji Oil Co., Ltd.), increased the localization of mRNA in the nucleus, indicating that it contains an inhibitor of mRNA processing [36].…”

Section: Resultsmentioning

confidence: 99%

“…In the first assay, 2 x 10 4 RLM1 cells previously established were inoculated in a 24-well plate and cultured for 24 h [35,37]. Sample was added in the culture media for 24 h. The cells were washed with phosphate-buffered saline (PBS) and lysed by passive lysis buffer (Promega, Madison, WI) for 30 min.…”

Section: Measurement Of Renilla Luciferase Activitymentioning

confidence: 99%

“…Cells were washed for 20 min at 42°C with 2x SSC, 0.5x SSC, and 0.1x SSC, respectively. The nuclei were visualized with 4', 6-diamidino-2-phenylindole (DAPI) [35,38]. Quantification of the ratio of nuclear and cytoplasmic poly (A) + RNA signals was calculated with ImageJ software (https://imagej.nih.gov/ij/) according to the instructions.…”

Section: U2os Cells (5 X 10mentioning

confidence: 99%

“…Previously, a monitoring system which is suitable for the screening of a wide range of chemical compounds that regulate mRNA processing has been established [35]. The first assay evaluates the activity of intron-containing Renilla luciferase reporter.…”

Section: Introductionmentioning

confidence: 99%

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Inhibition of mRNA Maturation by Compounds Which Have a Flavonoid Skeleton

Kurata¹,

Morimoto²,

Kawamura³

et al. 2017

BMB

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Post-transcriptional modifications of nascent mRNA include 5' capping, splicing and 3' end polyadenylation, resulting in the emergence of mature mRNA. Recent findings indicate that mRNA splicing inhibitors can be potential anti-cancer candidates. Soy-isoflavone fractions displayed an inhibitory effect of mRNA processing among a number of dietary components. Two major components of the isoflavone fraction, daidzin and genistin did not have an inhibitory activity against mRNA maturation. The aglycone form of them also failed to inhibit mRNA maturation. Instead, compounds with flavone skeleton inhibited the mRNA maturation in the nucleus. Considering that the structural difference between flavone and isoflavone compounds is that B-ring is attached either on the 2' or 3' position of C-ring, respectively, anti-mRNA maturation activity may require a defined structural basis. These data indicate that compounds with flavone skeleton specifically alter the mRNA processing step.

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Section: Resultsmentioning

confidence: 99%

Section: Measurement Of Renilla Luciferase Activitymentioning

confidence: 99%

Section: U2os Cells (5 X 10mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Inhibition of mRNA Maturation by Compounds Which Have a Flavonoid Skeleton

Kurata¹,

Morimoto²,

Kawamura³

et al. 2017

BMB

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show abstract

“…In our established method, a relatively moderate inhibitory effect on mRNA processing can be captured as bulk poly(A) + RNA accumulation in the nucleus (Fujita et al, 2012;Fujiwara et al, 2010). Utilizing our method, we previously screened food-derived compounds and identified mRNA processing inhibition activities in the soybean-derived isoflavonoid fraction and performed further analysis that elucidated that this activity was mainly exerted by compounds with a flavone skeleton (Kurata et al, 2016(Kurata et al, , 2017.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2019

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Cancer cells often exhibit 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 a 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 poly(A) + RNAs in these flavonoid-treated cells. Tumorigenic cells are more susceptible to these flavonoids than nontumorigenic 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 that were demonstrated by previous studies and provides the potential of daily intake of moderate splicing inhibitors to prevent cancer development.

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

et al. 2019

Self Cite

View full text Add to dashboard Cite

SummaryCancer cells often exhibit 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 a 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 poly(A)+ RNAs in these flavonoid-treated cells. Tumorigenic cells are more susceptible to these flavonoids than nontumorigenic 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 that were demonstrated by previous studies and provides the potential of daily intake of moderate splicing inhibitors to prevent cancer development.

show abstract

Establishment of a Monitoring System to Detect Inhibition of mRNA Processing

Cited by 8 publications

References 11 publications

Inhibition of mRNA Maturation by Compounds Which Have a Flavonoid Skeleton

Inhibition of mRNA Maturation by Compounds Which Have a Flavonoid Skeleton

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

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

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