Re-analysis of CLAP supports prior evidence of PRC2 as an RNA-binding protein
- 1Department of Genetics, Harvard Medical School, Boston, MA, USA
- 2Department of Molecular Biology, Massachusetts General Hospital, Boston, MA, USA
- 3Institute of Nanotechnology and Advanced Materials, The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel
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.
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BibTeX
@article{lee2026reanalysis,
title = {{Re-analysis of CLAP supports prior evidence of PRC2 as an RNA-binding protein}},
author = {YongWoo Lee and Priyojit Das and Barry Kesner and Michael Rosenberg and Roy Blum and Jeannie T. Lee},
journal = {Patterns},
year = {2026},
month = aug,
doi = {10.1016/j.patter.2026.101641},
url = {https://doi.org/10.1016/j.patter.2026.101641},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Re-analysis of CLAP supports prior evidence of PRC2 as an RNA-binding protein
AU - YongWoo Lee
AU - Priyojit Das
AU - Barry Kesner
AU - Michael Rosenberg
AU - Roy Blum
AU - Jeannie T. Lee
PY - 2026
DA - 2026/08/01
JO - Patterns
DO - 10.1016/j.patter.2026.101641
UR - https://doi.org/10.1016/j.patter.2026.101641
AB - 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.
SN - 2666-3899
ER -