Fig. 6

HSF-1 is required for full induction of numr-1. a Representative fluorescence and DIC micrographs of worms expressing numr-1p::GFP fed control or hsf-1 dsRNA and treated with 0 (control) or 100 μM cadmium for 24 h. Eight worms are shown in each image; scale bar is 100 μm. Fold changes in numr-1 (b), mtl-2 (b), or heat shock protein gene (c) mRNA levels in N2 worms fed control or hsf-1 dsRNA and treated with 0 (control) or 100 μM cadmium for 24 h as measured by qPCR. For b and c, N = 4 replicates of 200–300 worms. **P< 0.01 or ***P < 0.001 compared to control;control(RNAi) and ^‡P < 0.001 compared to cadmium;control(RNAi) as determined by two-way ANOVA with Bonferroni post hoc tests. d Lifespan of N2 worms fed control or hsf-1 dsRNA grown in the absence (control) or presence of 300 μM cadmium starting on day 1 of adulthood. Combined results are shown and statistics for individual trials are listed in Additional file 15: Table S9. The control data are the same as in Fig. 3c, d and listed in Additional file 4: Table S3. e Fold change in heat shock protein gene mRNAs in N2 worms fed with control, ints-2, ints-4, ints-5, ints-7, or ints-8 dsRNA. ***P < 0.001 compared to control dsRNA as determined by two-way ANOVA with Bonferroni post hoc tests, N = 4 replicates with each replicate containing 200–300 worms. f Proposed model. Cadmium disrupts RNA splicing in part via RNA processing by the integrator complex as evident by a change in snRNA. Following integrator complex disruption, an hsf-1-dependent transcriptional response is activated to induce the expression of small heat shock protein genes and an RRM-like domain containing gene named numr-1 that promotes RNA splicing, longevity, and stress resistance