Dual function of UPF3B in early and late translation termination

• Gabriele Neu‐Yilik ^[1] ; Etienne Raimondeau ^[2] ; Boris Eliseev ^[2] ; Lahari Yeramala ^[2] ; Beate Amthor ^[3] ; Aurélien Deniaud ^[2] ; Karine Huard ^[2] ; Kathrin Kerschgens ^[3] ; Matthias W Hentze ^[4] ; Christiane Schaffitzel ^[5] ; Andreas E Kulozik ^[1]
  1. [1] 1 Department of Pediatric Oncology, Hematology and Immunology University of Heidelberg Heidelberg Germany; 2 Molecular Medicine Partnership Unit University of Heidelberg and European Molecular Biology Laboratory Heidelberg Germany; 3 Hopp Kindertumorzentrum am NCT Heidelberg Heidelberg Germany
  2. [2] 4 European Molecular Biology Laboratory Grenoble France
  3. [3] 1 Department of Pediatric Oncology, Hematology and Immunology University of Heidelberg Heidelberg Germany; 2 Molecular Medicine Partnership Unit University of Heidelberg and European Molecular Biology Laboratory Heidelberg Germany
  4. [4] 2 Molecular Medicine Partnership Unit University of Heidelberg and European Molecular Biology Laboratory Heidelberg Germany; 5 European Molecular Biology Laboratory Heidelberg Germany
  5. [5] 4 European Molecular Biology Laboratory Grenoble France; 6 School of Biochemistry University of Bristol Bristol UK

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• Localización: EMBO journal: European Molecular Biology Organization, ISSN 0261-4189, Vol. 36, Nº. 20, 2017, págs. 2968-2986
• Idioma: inglés
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  • Nonsense‐mediated mRNA decay (NMD) is a cellular surveillance pathway that recognizes and degrades mRNAs with premature termination codons (PTCs). The mechanisms underlying translation termination are key to the understanding of RNA surveillance mechanisms such as NMD and crucial for the development of therapeutic strategies for NMD‐related diseases. Here, we have used a fully reconstituted in vitro translation system to probe the NMD proteins for interaction with the termination apparatus. We discovered that UPF3B (i) interacts with the release factors, (ii) delays translation termination and (iii) dissociates post‐termination ribosomal complexes that are devoid of the nascent peptide. Furthermore, we identified UPF1 and ribosomes as new interaction partners of UPF3B. These previously unknown functions of UPF3B during the early and late phases of translation termination suggest that UPF3B is involved in the crosstalk between the NMD machinery and the PTC‐bound ribosome, a central mechanistic step of RNA surveillance.