Ribosome-bound Upf1 forms distinct 80S complexes and conducts mRNA surveillance
UMass Chan AffiliationsMicrobiology and Physiological Systems
Morningside Graduate School of Biomedical Sciences
Document TypeJournal Article
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AbstractUpf1, Upf2, and Upf3, the central regulators of nonsense-mediated mRNA decay (NMD), appear to exercise their NMD functions while bound to elongating ribosomes, and evidence for this conclusion is particularly compelling for Upf1. Hence, we used selective profiling of yeast Upf1:ribosome association to define that step in greater detail, understand whether the nature of the mRNA being translated influences Upf1:80S interaction, and elucidate the functions of ribosome-associated Upf1. Our approach has allowed us to clarify the timing and specificity of Upf1 association with translating ribosomes, obtain evidence for a Upf1 mRNA surveillance function that precedes the activation of NMD, identify a unique ribosome state that generates 37-43 nt ribosome footprints whose accumulation is dependent on Upf1's ATPase activity, and demonstrate that a mutated form of Upf1 can interfere with normal translation termination and ribosome release. In addition, our results strongly support the existence of at least two distinct functional Upf1 complexes in the NMD pathway.
SourceGanesan R, Mangkalaphiban K, Baker RE, He F, Jacobson A. Ribosome-bound Upf1 forms distinct 80S complexes and conducts mRNA surveillance. RNA. 2022 Dec;28(12):1621-1642. doi: 10.1261/rna.079416.122. Epub 2022 Oct 3. PMID: 36192133; PMCID: PMC9670811.
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/51744
Rights© 2022 Ganesan et al. This article, published in RNA, is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/ by-nc/4.0/.; Attribution-NonCommercial 4.0 International
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Except where otherwise noted, this item's license is described as © 2022 Ganesan et al. This article, published in RNA, is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/ by-nc/4.0/.; Attribution-NonCommercial 4.0 International