Upf1 ATPase-Dependent mRNP Disassembly Is Required for Completion of Nonsense- Mediated mRNA Decay

SummaryCellular mRNAs exist in messenger ribonucleoprotein (mRNP) complexes, which undergo transitions during the lifetime of the mRNAs and direct posttranscriptional gene regulation. A final posttranscriptional step in gene expression is the turnover of the mRNP, which involves degradation of the mRNA and recycling of associated proteins. How tightly associated protein components are released from degrading mRNPs is unknown. Here, we demonstrate that the ATPase activity of the RNA helicase Upf1 allows disassembly of mRNPs undergoing nonsense-mediated mRNA decay (NMD). In the absence of Upf1 ATPase activity, partially degraded NMD mRNA intermediates accumulate in complex with NMD factors and concentrate in processing bodies. Thus, disassembly and completion of turnover of mRNPs undergoing NMD requires ATP hydrolysis by Upf1. This uncovers a previously unappreciated and potentially regulated step in mRNA decay and raises the question of how other mRNA decay pathways release protein components of substrate mRNPs.PaperFlick To view the video inline, enable JavaScript on your browser. However, you can download and view the video by clicking on the icon belowHelp with MP4 filesOptionsDownload video (22879 K)

Graphical AbstractFigure optionsDownload high-quality image (375 K)Download as PowerPoint slideHighlights
► Completion of nonsense-mediated mRNA decay (NMD) requires Upf1 ATPase activity
► Partially degraded NMD mRNP intermediates accumulate in the absence of Upf1 ATPase
► NMD mRNP intermediates are resistant to 5′-to-3′ exonucleolytic decay
► NMD mRNP intermediates accumulate in processing bodies