Inducible and reversible RNA N⁶-methyladenosine editing.

Abstract

RNA modifications, including N⁶-methyladenosine (m⁶A), have been reported to regulate fundamental RNA processes and properties, and directly linked to various human diseases. Methods enabling temporal and transcript/locus-specific editing of specific RNA modifications are essential, but still limited, to dissect the dynamic and context-dependent functions of these epigenetic modifications. Here, we develop a chemically inducible and reversible RNA m⁶A modification editing platform integrating chemically induced proximity (CIP) and CRISPR methods. We show that m⁶A editing can be temporally controlled at specific sites of individual RNA transcripts by the addition or removal of the CIP inducer, abscisic acid (ABA), in the system. By incorporating a photo-caged ABA, a light-controlled version of m⁶A editing platform can be developed. We expect that this platform and strategy can be generally applied to edit other RNA modifications in addition to m⁶A.