Adenylate cyclases are synthetic lethal with FH in HEK293T cells. (A) Expression levels of adenylate cyclase genes in HEK293T cells. (B) Ratios of shRNAs targeting all ten known adenylate cyclase genes, as determined from the primary screen. Ratios indicate the abundance of a certain shRNA under siFH vs siCTRL conditions. Negative values indicate depletion, positive values indicate enrichment. Dotted line indicates threshold defined by the distribution of twenty-one negative control shRNAs in order to distinguish background noise from real hits. For genes marked in blue, at least half of the shRNA agents targeting them were depleted below threshold and hence these genes were considered synthetic lethal with FH. shRNA dot colors: yellow: synthetic rescue, black: no synthetic effect, blue: synthetic lethal. (C) Viability of FH-impaired HEK293T cells (shFH) and HEK293T expressing endogenous levels of FH (shCTRL) determined after 6 days of expression of indicated shRNA. HEK293T cells were co-transduced with shFH and shADCY shRNA expression constructs or controls, respectively. (D) Residual mRNA level of targeted genes after 6 days of expression of indicated shRNA.