The GTP-binding release factor eRF3 as a key mediator coupling translation termination to mRNA decay.
GTP is essential for eukaryotic translation termination, where the release factor 3 (eRF3) complexed with eRF1 is involved as the guanine nucleotide-binding protein. In addition, eRF3 regulates the termination-coupled events, eRF3 interacts with poly(A)-binding protein (Pab1) and the surveillance factor Upf1 to mediate normal and nonsense-mediated mRNA decay. However, the roles of GTP binding to eRF3 in these processes remain largely unknown. Here, we showed in yeast that GTP is essentially required for the association of eRF3 with eRF1, but not with Pab1 and Upf1. A mutation in the GTP-binding motifs of eRF3 impairs the eRF1-binding ability without altering the Pab1- or Upf1-binding activity. Interestingly, the mutation causes not only a defect in translation termination but also delay of normal and nonsense-mediated mRNA decay, suggesting that GTP/eRF3-dependent termination exerts its influence on the subsequent mRNA degradation. The termination reaction itself is not sufficient, but eRF3 is essential for triggering mRNA decay. Thus, eRF3 is a key mediator that transduces termination signal to mRNA decay.
Kobayashi
Tetsuo
T
Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo 113-0033, Japan.
Funakoshi
Yuji
Y
Hoshino
Shin-Ichi
S
Katada
Toshiaki
T
D001665:Binding Sites; D006160:Guanosine Triphosphate / Q000378:metabolism*; D010454:Peptide Termination Factors / Q000502:physiology*; D039102:Poly(A)-Binding Proteins / Q000378:metabolism; D011328:Prions / Q000378:metabolism; D014176:Protein Biosynthesis; D020365:RNA Helicases / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins
D010454:Peptide Termination Factors; D039102:Poly(A)-Binding Proteins; D011328:Prions; D012333:RNA, Messenger; C068068:SUP35 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C450100:pab1 protein, S cerevisiae; C087971:peptide-chain-release factor 3; D006160:Guanosine Triphosphate; D020365:RNA Helicases