The fates of RNA species in a cell are controlled by ribonucleases, which 
degrade them by exploiting the universal structural 2'-OH group. This phenomenon 
plays a key role in numerous transformative technologies, for example, RNA 
interference and CRISPR/Cas13-based RNA editing systems. These approaches, 
however, are genetic or oligomer-based and so have inherent limitations. This 
has led to interest in the development of small molecules capable of degrading 
nucleic acids in a targeted manner. Here we describe click-degraders, small 
molecules that can be covalently attached to RNA species through click-chemistry 
and can degrade them, that are akin to ribonucleases. By using these molecules, 
we have developed the meCLICK-Seq (methylation CLICK-degradation Sequencing) a 
method to identify RNA modification substrates with high resolution at intronic 
and intergenic regions. The method hijacks RNA methyltransferase activity to 
introduce an alkyne, instead of a methyl, moiety on RNA. Subsequent 
copper(I)-catalyzed azide-alkyne cycloaddition reaction with the click-degrader 
leads to RNA cleavage and degradation exploiting a mechanism used by endogenous 
ribonucleases. Focusing on N6-methyladenosine (m6A), meCLICK-Seq identifies 
methylated transcripts, determines RNA methylase specificity, and reliably maps 
modification sites in intronic and intergenic regions. Importantly, we show that 
METTL16 deposits m6A to intronic polyadenylation (IPA) sites, which suggests a 
potential role for METTL16 in IPA and, in turn, splicing. Unlike other methods, 
the readout of meCLICK-Seq is depletion, not enrichment, of modified RNA 
species, which allows a comprehensive and dynamic study of RNA modifications 
throughout the transcriptome, including regions of low abundance. The 
click-degraders are highly modular and so may be exploited to study any RNA 
modification and design new technologies that rely on RNA degradation.