Cryptic RNA-binding by PRC2 components EZH2 and SUZ12

Polycomb repressive complex 2 (PRC2) is a histone-modifying complex that di/tri-methylates histone H3 lysine 27 (H3K27), a mark of transcriptionally repressed chromatin. However, how PRC2 is specifically recruited to its target loci remains controversial, although it has been postulated that long non-coding RNAs (lncRNAs) can function as guides. Here we purified individual components of PRC2 from human cultured cells and found that EZH2 and SUZ12 can directly bind to RNAs. In agreement with recent evidence, our results support the notion that these two PRC2 subunits have RNA-binding activity, with general preference for longer RNAs. However, the length alone does not explain their cryptic substrate preference. Our data highlight the difficulty of characterizing the RNA-binding activity of PRC2.