1241-RNA Reinforces Mutant ENL Condensate Nucleation

This article describes how locally produced RNA transcripts facilitate the development of leukemia and Wilms tumors by reinforcing oncogenic condensates formed by mutant ENL proteins. While ENL mutations drive protein self-association, this study identifies a critical "third layer" of regulation where RNA binding via a specific basic patch in the YEATS domain promotes condensate nucleation at key genomic loci. These RNA-dependent assemblies increase transcriptional bursting and chromatin occupancy at oncogenic targets like the HOXA cluster, effectively surpassing the gene activation threshold required for tumorigenesis. Experimental disruption of this RNA-protein interaction significantly impairs leukemogenesis in mouse models and reduces cancerous gene expression. Ultimately, the findings establish nascent RNA as a vital cofactor that helps pathogenic proteins hijack the local chromatin environment to sustain malignant cell states.References:Budinich K A, Yao X, Gong C, et al. RNA reinforces condensate nucleation on chromatin to amplify oncogenic transcription[J]. bioRxiv, 2025: 2025.07. 29.665963.前往小宇宙评论区与主播互动