Ire1-mediated decay in mammalian cells relies on mRNA sequence, structure, and translational status Journal Article uri icon

Overview

abstract

  • 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.

publication date

  • August 15, 2015

Date in CU Experts

  • October 28, 2020 12:33 PM

Full Author List

  • Moore K; Hollien J

author count

  • 2

Other Profiles

International Standard Serial Number (ISSN)

  • 1059-1524

Electronic International Standard Serial Number (EISSN)

  • 1939-4586

Additional Document Info

start page

  • 2873

end page

  • 2884

volume

  • 26

issue

  • 16