Caenorhabditis elegans HSF ‐1 is an essential nuclear protein that forms stress granule‐like structures following heat shock

Summary The heat shock transcription factor ( HSF ) is a conserved regulator of heat shock‐inducible gene expression. Organismal roles for HSF in physiological processes such as development, aging, and immunity have been defined largely through studies of the single Caenorhabditis elegans HSF homolog, hsf‐1 . However, the molecular and cell biological properties of hsf‐1 in C. elegans are incompletely understood. We generated animals expressing physiological levels of an HSF ‐1:: GFP fusion protein and examined its function, localization, and regulation in vivo . HSF ‐1:: GFP was functional, as measured by its ability to rescue phenotypes associated with two hsf‐1 mutant alleles. Rescue of hsf‐1 development phenotypes was abolished in a DNA ‐binding‐deficient mutant, demonstrating that the transcriptional targets of hsf‐1 are critical to its function even in the absence of stress. Under nonstress conditions, HSF ‐1:: GFP was found primarily in the nucleus. Following heat shock, HSF ‐1:: GFP rapidly and reversibly redistributed into dynamic, subnuclear structures that share many properties with human nuclear stress granules, including colocalization with markers of active transcription. Rapid formation of HSF ‐1 stress granules required HSF ‐1 DNA ‐binding activity, and the threshold for stress granule formation was altered by growth temperature. HSF ‐1 stress granule formation was not induced by inhibition of IGF signaling, a pathway previously suggested to function upstream of hsf‐1 . Our findings suggest that development, stress, and aging pathways may regulate HSF ‐1 function in distinct ways, and that HSF ‐1 nuclear stress granule formation is an evolutionarily conserved aspect of HSF ‐1 regulation in vivo .