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

ABSTRACT: 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)⁺

SUBMITTER: Kurata M 

PROVIDER: S-EPMC6909097 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature