Journal
MOLECULAR BIOLOGY OF THE CELL
Volume 26, Issue 16, Pages 2873-2884Publisher
AMER SOC CELL BIOLOGY
DOI: 10.1091/mbc.E15-02-0074
Keywords
-
Categories
Ask authors/readers for more resources
Endoplasmic reticulum (ER) stress occurs when misfolded proteins overwhelm the capacity of the ER, resulting in activation of the unfolded protein response (UPR). Ire1, an ER transmembrane nuclease and conserved transducer of the UPR, cleaves the mRNA encoding the transcription factor Xbp1 at a dual stem-loop (SL) structure, leading to Xbp1 splicing and activation. Ire1 also cleaves other mRNAs localized to the ER membrane through regulated Ire1-dependent decay (RIDD). We find that during acute ER stress in mammalian cells, Xbp1-like SLs within the target mRNAs are necessary for RIDD. Furthermore, depletion of Perk, a UPR transducer that attenuates translation during ER stress, inhibits RIDD in a substrate-specific manner. Artificially blocking translation of the SL region of target mRNAs fully restores RIDD in cells depleted of Perk, suggesting that ribosomes disrupt SL formation and/or Ire1 binding. This coordination between Perk and Ire1 may serve to spatially and temporally regulate RIDD.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available