Inhibition of mRNA Maturation by Compounds Which Have a Flavonoid Skeleton

Abstract

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.

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

“…Previously, we identified several flavonoids that have inhibitory activity against mRNA processing (Kurata et al., 2016, Kurata et al., 2017). In this study, we explored the structure-activity relationship of compounds with a flavone skeleton by RNA-FISH (Figures 1 and S1).…”

“…Despite the broad bioactivity of flavonoids, few studies on their regulatory activity against mRNA processing, especially splicing, have been reported. We previously searched for compounds derived from food that have the ability to inhibit mRNA processing and identified such effects in compounds with a flavone skeleton (Kurata et al., 2016, Kurata et al., 2017).…”

“…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).…”

Regulating Divergent Transcriptomes through mRNA Splicing and Its Modulation Using Various Small Compounds

“…We examined whether food-derived compounds provide inhibitory activity toward mRNA processing in the nucleus using a previously established screening system [199,200]. We identified the activity of inhibiting mRNA processing in the soybean-derived isoflavonoid fraction [200,201]. Furthermore, this activity was mainly exerted by compounds with a flavone skeleton [200].…”

“…We identified the activity of inhibiting mRNA processing in the soybean-derived isoflavonoid fraction [200,201]. Furthermore, this activity was mainly exerted by compounds with a flavone skeleton [200]. Among them, apigenin and luteolin exhibited the strongest activity among 21 compounds with a flavone skeleton [202].…”