Abstract
Cells adapt to environmental stress by reprogramming gene expression. During heat stress, the transcription factor heat shock factor 1 (HSF1) translocates into the nucleus and activates heat shock-responsive loci, including the long non-coding RNA HSATIII, promoting nuclear stress body (nSB) formation. We show that the Mediator complex subunit MED26 enhances HSATIII transcription and nSB formation through a mechanism distinct from its role at heat-shock response (HSR) genes. Under heat stress, MED26-containing Mediator is recruited to HSR genes and nSBs through interactions with HSF1 and MED15. Phosphorylation of the intrinsically disordered region of HSF1 appears to facilitate Mediator recruitment to nSBs. Acute loss of MED26 leads to the dissociation of the Mediator and RNA polymerase II (Pol II) from HSR gene promoters, whereas the Mediator remains bound to HSATIII despite Pol II dissociation. These results suggest that MED26 acts as molecular switch, thereby facilitating Mediator-Pol II complex assembly at nSBs and promoting nSB formation during heat stress.

Highlights
・MED26 relocates from Cajal bodies to nuclear stress bodies upon heat stress
・HSF1 recruits MED26-containing Mediator through MED15 during heat stress
・Mediator recruitment differs between HSATIII and HSR genes
・MED26 facilitates Mediator-Pol II assembly to drive nuclear stress body formation