Work

Re-analysis of CLAP supports prior evidence of PRC2 as an RNA-binding protein

Year: 2026

Type: article

Abstract: Using CLAP methodology, Guo et al. recently concluded that PRC2 is not an RNA binding protein (RBP). They suggest that prior findings were CLIP artifacts and argue against RNA's direct role in PRC2 regulation. Here, we re-analyze their raw datasets and reach contrary conclusions. Through an independent computational pipeline, we observe significant PRC2 enrichment throughout the transcriptome, including XIST. Applying the authors' published computational pipeline also reaffirms PRC2 as an RBP. Detailed investigation of the authors' pipeline reveals several unconventional practices. First, Guo et al. retained reads from foreign species and other unmappable reads to obtain a normalization factor. Second, they selectively removed read duplicates from the mappable fraction, while retaining them in the unmappable fraction. Finally, the authors applied an arbitrary cutoff for enrichment values in XIST. Their pipeline thereby inflated PRC2's background reads and suppressed mappable signals, creating the impression that PRC2 is not a robust RBP.

Source: Patterns

DOI: 10.1016/j.patter.2026.101641

Authors: YongWoo Lee, Priyojit Das, Barry Kesner, Michael Rosenberg, Roy Blum, Jeannie T. Lee

Institutions: Harvard University, Massachusetts General Hospital, Bar-Ilan University

Language: English

Topic: RNA Research and Splicing

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: gold

Estimated APC paid: $4,900

Funders: National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development