Genome-scale Activation of LncRNA Loci Identifies Novel Vemurafenib Resistance Mediators
Mammalian genomes transcribe thousands of lncRNAs, most of whose functions are unknown. We developed a CRISPR-Cas9 activation screen of >10,000 lncRNAs to identify noncoding loci that mediate BRAF inhibitor resistance in melanoma. We find 11 novel lncRNA loci, including one we term EMICERI. We functionally dissect the EMICERI locus to demonstrate that activation of EMICERI results in dosage-dependent activation of its four neighboring genes, including a kinase activator MOB3B, and that the resistance phenotype arises from MOB3B overexpression.