ATP hydrolysis by UPF1 is required for efficient translation termination at premature stop codons
| Autor: | Kristian E. Baker, Da Juan L Whiteside, Lucas D Serdar |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Saccharomyces cerevisiae Proteins RNA Stability Science Nonsense mutation General Physics and Astronomy Saccharomyces cerevisiae Ribosome Models Biological General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences Adenosine Triphosphate ATP hydrolysis Polysome RNA Messenger Adenosine Triphosphatases Messenger RNA Multidisciplinary Chemistry Hydrolysis RNA General Chemistry Peptide Chain Termination Translational RNA Helicase A Molecular biology Stop codon Cell biology 030104 developmental biology Codon Nonsense Polyribosomes Mutation RNA Helicases |
| Zdroj: | Nature Communications, Vol 7, Iss 1, Pp 1-8 (2016) Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | Nonsense-mediated mRNA decay (NMD) represents a eukaryotic quality control pathway that recognizes and rapidly degrades transcripts harbouring nonsense mutations to limit accumulation of non-functional and potentially toxic truncated polypeptides. A critical component of the NMD machinery is UPF1, an RNA helicase whose ATPase activity is essential for NMD, but for which the precise function and site of action remain unclear. We provide evidence that ATP hydrolysis by UPF1 is required for efficient translation termination and ribosome release at a premature termination codon. UPF1 ATPase mutants accumulate 3′ RNA decay fragments harbouring a ribosome stalled during premature termination that impedes complete degradation of the mRNA. The ability of UPF1 to impinge on premature termination, moreover, requires ATP-binding, RNA-binding and NMD cofactors UPF2 and UPF3. Our results reveal that ATP hydrolysis by UPF1 modulates a functional interaction between the NMD machinery and terminating ribosomes necessary for targeting substrates to accelerated degradation. Nonsense-mediated mRNA decay (NMD) is a quality control pathway that recognizes and degrades transcripts harbouring nonsense mutations. Here the authors show that the ATPase activity of UPF1 mediates functional interactions between the NMD machinery and ribosomes required for efficient ribosome release at premature termination codons. |
| Databáze: | OpenAIRE |
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