Optogenetic Clustering of Human IRE1 Reveals Differential Regulation of Transcription and mRNA Splice Isoform Abundance by the UPR.

ABSTRACT: Inositol-requiring enzyme 1 (IRE1) is one of three known sensor proteins that respond to homeostatic perturbations in the metazoan endoplasmic reticulum. The three sensors collectively initiate an intertwined signaling network called the Unfolded Protein Response (UPR). Although IRE1 plays pivotal roles in human health and development, understanding its specific contributions to the UPR remains a challenge due to signaling crosstalk from the other two stress sensors. To overcome this problem, we engineered a light-activatable version of IRE1 and probed the transcriptomic effects of IRE1 activity in isolation from the other branches of the UPR. We demonstrate that 1) oligomerization alone is sufficient to activate IRE1 in human cells, 2) IRE1's transcriptional response evolves substantially

SUBMITTER: Smith JW 

PROVIDER: S-EPMC12330662 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature