Re-analysis of CLAP data affirms PRC2 as an RNA binding protein.

Using halo-tagged PRC2 and "CLAP" methodology, Guo et al. recently came to the conclusion that PRC2 is not an RNA binding protein (RBP). They suggested that previous findings are CLIP artifacts and argue that RNA cannot play a direct role in PRC2 regulation. Here, we perform a re-analysis of the authors' raw datasets and come to contrary conclusions. First, CLAP demonstrates significant PRC2 enrichment throughout the transcriptome, including in XIST's Repeat A (RepA) motif. Second, our re-analysis of the authors' CLAP and CLIP datasets demonstrates that the two methods yield similar outcomes, with both showing PRC2 enrichment in the transcriptome. Furthermore, PRC2 demonstrates more RNA binding peaks than SAF-A and PTBP1. Additionally, re-analysis of CLAP contradicts the authors' conclusion that CTCF and YY1 are not RBP. The discrepancies may be attributable to the authors' unconventional data normalization, methods of determining significance, and lack of minus-tag and input controls in some experiments.