RIOK1 kinase activity is required for cell survival irrespective of status.

Genotype specific vulnerabilities of cancer cells constitute a promising strategy for the development of new therapeutics. Deletions of non-essential genes in tumors can generate unique vulnerabilities which could be exploited therapeutically. The gene is recurrently deleted in human cancers because of its chromosomal proximity to the tumor suppressor gene . Recent studies have uncovered an increased dependency of -deleted cancer cells on the function of a PRMT5 containing complex, including WDR77, PRMT5 and the kinase RIOK1. As RIOK1 kinase activity constitutes a potential therapeutic target, we wanted to test if deletion confers increased sensitivity to RIOK1 inhibition. Using CRISPR/Cas9-mediated genome engineering we generated analog sensitive alleles of in isogenic cell lines differing only by status. While we were able to independently confirm an increased dependency of -deleted cells on PRMT5, we did not detect a differential requirement for RIOK1 kinase activity between -proficient and deficient cells. Our results reveal that the kinase activity of RIOK1 is required for the survival of cancer cell lines irrespective of their status and cast doubt on the therapeutic exploitability of RIOK1 in the context of -deleted cancers.