A conformational RNA zipper promotes intron ejection during non-conventional XBP1 mRNA splicing.

TitleA conformational RNA zipper promotes intron ejection during non-conventional XBP1 mRNA splicing.
Publication TypeJournal Article
Year of Publication2015
AuthorsPeschek J, Acosta-Alvear D, Mendez AS, Walter P
JournalEMBO Rep
Volume16
Issue12
Pagination1688-98
Date Published2015 Dec
ISSN1469-3178
KeywordsAnimals, Base Sequence, Conserved Sequence, DNA-Binding Proteins, Endoplasmic Reticulum, Endoribonucleases, Humans, Introns, Nucleic Acid Conformation, Protein Folding, Protein-Serine-Threonine Kinases, RNA Splicing, RNA, Messenger, Sequence Alignment, Sequence Analysis, DNA, Transcription Factors, Transcription, Genetic, Unfolded Protein Response
Abstract

The kinase/endonuclease IRE1 is the most conserved signal transducer of the unfolded protein response (UPR), an intracellular signaling network that monitors and regulates the protein folding capacity of the endoplasmic reticulum (ER). Upon sensing protein folding perturbations in the ER, IRE1 initiates the unconventional splicing of XBP1 mRNA culminating in the production of the transcription factor XBP1s, which expands the ER's protein folding capacity. We show that an RNA-intrinsic conformational change causes the intron of XBP1 mRNA to be ejected and the exons to zipper up into an extended stem, juxtaposing the RNA ends for ligation. These conformational rearrangements are important for XBP1 mRNA splicing in vivo. The features that point to such active participation of XBP1 mRNA in the splicing reaction are highly conserved throughout metazoan evolution, supporting their importance in orchestrating XBP1 mRNA processing with efficiency and fidelity.

DOI10.15252/embr.201540955
Alternate JournalEMBO Rep.
PubMed ID26483401
PubMed Central IDPMC4687415
Grant List / / Howard Hughes Medical Institute / United States