Regulation of sumo mRNA during endoplasmic reticulum stress.
The unfolded protein response (UPR) is a collection of pathways that maintains the protein secretory pathway during the many physiological and pathological conditions that cause stress in the endoplasmic reticulum (ER). The UPR is mediated in part by Ire1, an ER transmembrane kinase and endoribonuclease that is activated when misfolded proteins accumulate in the ER. Ire1's nuclease initiates the cytosolic splicing of the mRNA encoding X-box binding protein (Xbp1), a potent transcription factor that then upregulates genes responsible for restoring ER function. This same nuclease is responsible for the degradation of many other mRNAs that are localized to the ER, through Regulated Ire1 Dependent Decay (RIDD). Here we show that Smt3, a homolog of small ubiquitin-like modifier (sumo), is a non-canonical RIDD target in Drosophila S2 cells. Unlike other RIDD targets, the sumo transcript does not stably associate with the ER membrane, but instead relies on an Xbp1-like stem loop and a second UPR mediator, Perk, for its degradation during stress.
Department of Biology and the Center for Cell and Genome Science, University of Utah, Salt Lake City, Utah, United States of America.
Kristin A
KA
Moore
Joshua J
JJ
Plant
Deepika
D
Gaddam
Jonathan
J
Craft
Julie
J
Hollien
D000818:Animals; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster; D004721:Endoplasmic Reticulum / Q000235:genetics / Q000378:metabolism*; D004722:Endoribonucleases / Q000235:genetics / Q000378:metabolism; D020871:RNA Stability / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000096:biosynthesis* / Q000235:genetics; D025841:Small Ubiquitin-Related Modifier Proteins; D056811:Unfolded Protein Response / Q000502:physiology*
D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; D025841:Small Ubiquitin-Related Modifier Proteins; C517798:Xbp1 protein, Drosophila; C490960:smt3 protein, Drosophila; D004722:Endoribonucleases; C511918:inositol requiring enzyme-1, Drosophila