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Identification of a localized nonsense-mediated decay pathway at the endoplasmic reticulum.

Abstract：

: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.

journal_name

Genes Dev

journal_title

Genes & development

authors

Longman D,Jackson-Jones KA,Maslon MM,Murphy LC,Young RS,Stoddart JJ,Hug N,Taylor MS,Papadopoulos DK,Cáceres JF

doi

10.1101/gad.338061.120

subject

Has Abstract

pub_date

2020-08-01 00:00:00

pages

1075-1088

issue

15-16

eissn

0890-9369

issn

1549-5477

pii

gad.338061.120

journal_volume

34

pub_type

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