CRISPR mutagenesis of the MYC locus reveals a druggable ultraconserved RNA element.

CRISPR tiling mutagenesis of the 10-kb human MYC locus identifies an ultraconserved 3' UTR RNA element that promotes MYC mRNA perinuclear localization and MYC protein nuclear localization.

• Why it matters: Noncoding DNA makes up most of the genome, but which parts are functionally essential—and druggable—has remained unclear.
• What they did: Using near-PAMless, high-fidelity SpRY-Cas9 CRISPR tiling mutagenesis, the authors mapped the MYC locus fitness landscape at base-pair resolution and tested an ultraconserved 3' UTR RNA element with hnRNP L interaction and steric-blocking ASOs.
• The result: ASO targeting of the element selectively eliminates diverse MYC-dependent cancer cells and inhibits growth of patient-derived tumor organoids, supporting noncoding sequences as major functional genetic information carriers.

AI summary of the abstract · may contain errors · not medical advice · read the paper.