Translation termination depends on the sequential ribosomal entry of eRF1 and eRF3
2019 | journal article. A publication with affiliation to the University of Göttingen.
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- Authors
- Beissel, Christian ; Neumann, Bettina ; Uhse, Simon ; Hampe, Irene ; Karki, Prajwal ; Krebber, Heike
- Abstract
- Translation termination requires eRF1 and eRF3 for polypeptide- and tRNA-release on stop codons. Additionally, Dbp5/DDX19 and Rli1/ABCE1 are required; however, their function in this process is currently unknown. Using a combination of in vivo and in vitro experiments, we show that they regulate a stepwise assembly of the termination complex. Rli1 and eRF3-GDP associate with the ribosome first. Subsequently, Dbp5-ATP delivers eRF1 to the stop codon and in this way prevents a premature access of eRF3. Dbp5 dissociates upon placing eRF1 through ATP-hydrolysis. This in turn enables eRF1 to contact eRF3, as the binding of Dbp5 and eRF3 to eRF1 is mutually exclusive. Defects in the Dbp5-guided eRF1 delivery lead to premature contact and premature dissociation of eRF1 and eRF3 from the ribosome and to subsequent stop codon readthrough. Thus, the stepwise Dbp5-controlled termination complex assembly is essential for regular translation termination events. Our data furthermore suggest a possible role of Dbp5/DDX19 in alternative translation termination events, such as during stress response or in developmental processes, which classifies the helicase as a potential drug target for nonsense suppression therapy to treat cancer and neurodegenerative diseases.
- Issue Date
- 2019
- Journal
- Nucleic Acids Research
- ISSN
- 0305-1048; 1362-4962
- eISSN
- 1362-4962
- Language
- English