Translation termination depends on the sequential ribosomal entry of eRF1 and eRF3.

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.
Mesh Terms:
Codon, Terminator, DEAD-box RNA Helicases, Guanosine Triphosphate, Nucleocytoplasmic Transport Proteins, Peptide Chain Termination, Translational, Peptide Termination Factors, Protein Binding, Protein Biosynthesis, RNA, Transfer, Ribosomes, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins
Nucleic Acids Res
Date: Dec. 21, 2018
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