The unfolded protein response and endoplasmic reticulum protein targeting machineries converge on the stress sensor IRE1.

TitleThe unfolded protein response and endoplasmic reticulum protein targeting machineries converge on the stress sensor IRE1.
Publication TypeJournal Article
Year of Publication2018
AuthorsAcosta-Alvear D, Karagöz GElif, Fröhlich F, Li H, Walther TC, Walter P
JournalElife
Volume7
Date Published2018 Dec 24
ISSN2050-084X
Abstract

The protein folding capacity of the endoplasmic reticulum (ER) is tightly regulated by a network of signaling pathways, known as the unfolded protein response (UPR). UPR sensors monitor the ER folding status to adjust ER folding capacity according to need. To understand how the UPR sensor IRE1 maintains ER homeostasis, we identified zero-length crosslinks of RNA to IRE1 with single nucleotide precision . We found that IRE1 specifically crosslinks to a subset of ER-targeted mRNAs, SRP RNA, ribosomal and transfer RNAs. Crosslink sites cluster in a discrete region of the ribosome surface spanning from the A-site to the polypeptide exit tunnel. Moreover, IRE1 binds to purified 80S ribosomes with high affinity, indicating association with ER-bound ribosomes. Our results suggest that the ER protein translocation and targeting machineries work together with the UPR to tune the ER's protein folding load.

DOI10.7554/eLife.43036
Alternate JournalElife
PubMed ID30582518
Grant ListInvestigator / / Howard Hughes Medical Institute / United States
Postdoctoral fellowship / / Cancer Research Institute /
Investigator / / Howard Hughes Medical Institute / United States