Identification of a localized nonsense-mediated decay pathway at the endoplasmic reticulum
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...
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Published in | Genes & development Vol. 34; no. 15-16; pp. 1075 - 1088 |
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Main Authors | , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Cold Spring Harbor Laboratory Press
01.08.2020
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Subjects | |
Online Access | Get full text |
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Summary: | 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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Present address: Centre for Global Health Research, Usher Institute, University of Edinburgh, Old Medical School, Edinburgh EH8 9AG, UK |
ISSN: | 0890-9369 1549-5477 |
DOI: | 10.1101/gad.338061.120 |