Extranuclear Epitranscriptomic Mechanisms Control Metastasis

Here, we show existence of ncRNAs and RNA binding proteins called “R-bodies” within the cytoplasm of metastatic cancer cells. Biogenesis of R-bodies begins with integrin activation and intracellular accumulation of proteases. m6A-epigenetically marked MALAT1 was exclusively found in R-bodies and determined to be the core for R-body formation.

Disabling R-bodies using METTL3 inhibitors and RNA therapy against m6A-MALAT1 were effective in halting cell invasion and metastasis dynamics. The extranuclear epitranscriptome unites extracellular and nuclear factors to swiftly induce cancer progression within hours. This is evidenced by the epigenome generating m6A-MALAT1 in the cytoplasm which goes onto cytoplasmic R-bodies, leading to cancer invasion.