Annibaldis, Giuditta; Domanski, Michal; Dreos, René; Contu, Lara; Carl, Sarah; Kläy, Nina; Mühlemann, Oliver (2020). Readthrough of stop codons under limiting ABCE1 concentration involves frameshifting and inhibits nonsense-mediated mRNA decay. Nucleic acids research, 48(18), pp. 10259-10279. Oxford University Press 10.1093/nar/gkaa758
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Annibaldis_NAR2020_FRameshift-associated readthrough and NMD inhibition in ABCE1 KD.pdf - Published Version Available under License Creative Commons: Attribution-Noncommercial (CC-BY-NC). Download (5MB) | Preview |
To gain insight into the mechanistic link between translation termination and nonsense-mediated mRNA decay (NMD), we depleted the ribosome recycling factor ABCE1 in human cells, resulting in an upregulation of NMD-sensitive mRNAs. Suppression of NMD on these mRNAs occurs prior to their SMG6-mediated endonucleolytic cleavage. ABCE1 depletion caused ribosome stalling at termination codons (TCs) and increased ribosome occupancy in 3' UTRs, implying enhanced TC readthrough. ABCE1 knockdown indeed increased the rate of readthrough and continuation of translation in different reading frames, providing a possible explanation for the observed NMD inhibition, since enhanced readthrough displaces NMD activating proteins from the 3' UTR. Our results indicate that stalling at TCs triggers ribosome collisions and activates ribosome quality control. Collectively, we show that improper translation termination can lead to readthrough of the TC, presumably due to ribosome collisions pushing the stalled ribosomes into the 3' UTR, where it can resume translation in-frame as well as out-of-frame.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
08 Faculty of Science > Department of Chemistry, Biochemistry and Pharmaceutical Sciences (DCBP) 08 Faculty of Science > Department of Chemistry, Biochemistry and Pharmaceutical Sciences (DCBP) > NCCR RNA & Disease |
Graduate School: |
Graduate School for Cellular and Biomedical Sciences (GCB) |
UniBE Contributor: |
Annibaldis, Giuditta, Domanski, Michal, Contu, Lara, Mühlemann, Oliver |
Subjects: |
500 Science > 570 Life sciences; biology 500 Science > 540 Chemistry |
ISSN: |
0305-1048 |
Publisher: |
Oxford University Press |
Language: |
English |
Submitter: |
Christina Schüpbach |
Date Deposited: |
18 Sep 2020 15:37 |
Last Modified: |
05 Dec 2022 15:40 |
Publisher DOI: |
10.1093/nar/gkaa758 |
BORIS DOI: |
10.7892/boris.146588 |
URI: |
https://boris.unibe.ch/id/eprint/146588 |
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