Extended Data Fig. 4: Characterization of SKIc loss and relationship with PELO.
From: Synthetic lethality of mRNA quality control complexes in cancer
(a) Guide level analysis of 9p21 genes. NCI-H1299 parent (orange) and PELO−/− (blue) models shown. Two-tailed Student’s t-test of n = 4 sgRNA per gene, Parent vs. PELO −/−; FOCAD, P = 5.7 × 10−3. (b) SL-ID screen results in SKIV2L −/− and FOCAD −/− models. NCI-H1299 parental (orange) SKIV2L −/− or FOCAD −/− (blue). Each dot represents an individual sgRNA (n = 4) for each gene, mean of n = 3 independent biological replicates. (c) Immunoblot of the PELO/HBS1L/ABCE1 rescue complex across isogenic SKIc knockout models. (d) PELO dependency by siRNA in HAP1 or HAP1 SKIV2L −/− models. Data shown as mean ± s.e.m, n = 3 biologically independent replicates, two-tailed Student’s t-test; P = 9.9 × 10−7. (e) Validation of siRNA efficiency by immunoblot in (d). Data generated from a single experiment. (f) RNA quantification of SKIc levels (FOCAD, TTC37, SKIV2L, AVEN) post FOCAD degradation. Data shown as mean ± s.e.m, n = 3 biologically independent replicates, two-tailed Student’s t-test. (g) sgWDR61 in NCI-H1299 parental, PELO −/−, and SKIV2L −/− models. Confluency of sgB2M (black), sgWDR61 (blue). Data shown as mean ± s.e.m, n = 3 biologically independent replicates (h) Immunoblot validation of sgWDR61 efficiency and effects on SKIc in models from (g). Data is generated from a single independent experiment.
