Identification of a localized Nonsense-Mediated Decay pathway at the Endoplasmic Reticulum

Dasa Longman, Kathryn Jackson-Jones, Magdalena Maslon, Laura Murphy, Robert Young, Jack Stoddart, Nele Hug, Martin Taylor, Dimitrios K Papadopoulos, Javier F. Caceres

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Nonsense-mediated decay (NMD) is a translation-dependent RNA quality control mechanism that occurs in the cytoplasm. However, it is unknown how NMD regulates the stability of RNAs translated at the endoplasmic reticulum (ER). Here, we identify a localized NMD pathway dedicated to ER-translated mRNAs. We previously identified NBAS, a component of the Syntaxin 18 complex involved in Golgi-to-ER trafficking, as a novel NMD factor. Furthermore, we show that NBAS fulfills an independent function in NMD. This ER–NMD pathway requires the interaction of NBAS with the core NMD factor UPF1, which is partially localized at the ER in the proximity of the translocon. NBAS and UPF1 coregulate the stability of ER-associated transcripts, in particular those associated with the cellular stress response. We propose a model where NBAS recruits UPF1 to the membrane of the ER and activates an ER-dedicated NMD pathway, thus providing an ER-protective function by ensuring quality control of ER-translated mRNAs.
Original languageEnglish
Pages (from-to)1075-1088
JournalGenes & Development
Issue number15-16
Early online date2 Jul 2020
Publication statusE-pub ahead of print - 2 Jul 2020

Keywords / Materials (for Non-textual outputs)

  • nonsense-mediated decay (NMD)
  • RNA quality control
  • UPF1
  • NBAS
  • ER stress
  • UPR


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