Comunicação direta entre a vigilância celular e a maquinaria sintetizadora de proteínas elimina erros genéticos: mero acaso, fortuita necessidade ou design inteligente???

quinta-feira, janeiro 12, 2017

ATP hydrolysis by UPF1 is required for efficient translation termination at premature stop codons

Lucas D. Serdar, DaJuan L. Whiteside & Kristian E. Baker

Nature Communications 7, Article number: 14021 (2016)


Download Citation

RibosomeRNA quality control

Received: 07 June 2016 Accepted: 22 November 2016 Published online: 23 December 2016


Abstract

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.

Author information

Affiliations

Center for RNA Molecular Biology, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA

Lucas D. Serdar, DaJuan L. Whiteside & Kristian E. Baker

Contributions

L.D.S. and K.E.B. conceived and designed the study; L.D.S. and D.L.W. performed the experiments; and L.D.S., D.L.W. and K.E.B. wrote the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Kristian E. Baker.