Human NMD ensues independently of stable ribosome stalling.

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Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_2EB67EC06977
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Human NMD ensues independently of stable ribosome stalling.
Journal
Nature communications
Author(s)
Karousis E.D., Gurzeler L.A., Annibaldis G., Dreos R., Mühlemann O.
ISSN
2041-1723 (Electronic)
ISSN-L
2041-1723
Publication state
Published
Issued date
17/08/2020
Peer-reviewed
Oui
Volume
11
Number
1
Pages
4134
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Abstract
Nonsense-mediated mRNA decay (NMD) is a translation-dependent RNA degradation pathway that is important for the elimination of faulty, and the regulation of normal, mRNAs. The molecular details of the early steps in NMD are not fully understood but previous work suggests that NMD activation occurs as a consequence of ribosome stalling at the termination codon (TC). To test this hypothesis, we established an in vitro translation-coupled toeprinting assay based on lysates from human cells that allows monitoring of ribosome occupancy at the TC of reporter mRNAs. In contrast to the prevailing NMD model, our in vitro system reveals similar ribosomal occupancy at the stop codons of NMD-sensitive and NMD-insensitive reporter mRNAs. Moreover, ribosome profiling reveals a similar density of ribosomes at the TC of endogenous NMD-sensitive and NMD-insensitive mRNAs in vivo. Together, these data show that NMD activation is not accompanied by stable stalling of ribosomes at TCs.
Keywords
3' Untranslated Regions/genetics, 3' Untranslated Regions/physiology, Codon, Terminator/genetics, Humans, Nonsense Mediated mRNA Decay/genetics, Nonsense Mediated mRNA Decay/physiology, RNA Stability/genetics, RNA Stability/physiology, RNA, Messenger/genetics, RNA, Messenger/metabolism, Ribosomes/genetics, Ribosomes/metabolism
Pubmed
Web of science
Open Access
Yes
Create date
28/08/2020 8:46
Last modification date
06/04/2024 7:27
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