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Native RNA immunoprecipitation (nRIP) coupled with high-throughput sequencing (nRIP-seq) is a powerful technique that allows transcriptome-wide identification of the entire subset of coding and noncoding RNAs associated with a particular protein. Since this technology is carried out in a native condition without cross-linking, nRIP-seq detects RNAs that bind a protein directly or indirectly through a larger RNA-protein complex. Here, we use the interaction between RNA and chromatin modifiers, Polycomb proteins, as an example to describe this method. Using nRIP-seq, we provide a snapshot of Ezh2, a Polycomb component, and RNA interaction in mouse embryonic stem cells.

nRIP-seq: A Technique to Identify RNA Targets of an RNA Binding Protein on a Genome-Wide Scale