Eukaryotic Release Factor (eRF)
Eukaryotic release factors terminate protein biosynthesis by recognizing stop codons and promoting peptidyl-tRNA hydrolysis on the ribosome[1][2]. Mechanistically, eRF1 recognizes UAA, UAG, and UGA stop codons, whereas eRF3 acts as a GTPase that cooperates with eRF1 to accelerate nascent polypeptide release[2][3]. In mRNA quality control, eRF1 and eRF3 also participate in the SMG1-UPF1-eRF1-eRF3 SURF complex that links translation termination to nonsense-mediated mRNA decay[4]. In disease models, premature termination codon readthrough provides an experimental route for studying nonsense-mutation disorders, and eRF3 degradation enhances G418-induced readthrough while altering NMD-related protein levels[5]. Compared with eRF3b, eRF3a silencing markedly increases premature nonsense codon readthrough in human cells, while eRF3b overexpression compensates for termination defects caused by eRF3a depletion[6]. Therefore, eRF3a and eRF3b are not fully equivalent release-factor isoforms, because eRF3a mainly maintains mammalian termination-complex formation and eRF1 stability[6]. For experimental applications, eRF3a degraders including CC-90009, CC-885, and SJ6986 support studies of premature stop codon readthrough and CFTR nonsense-mutation rescue[5][7].eRF research connects translation termination, stop codon recognition, GTP hydrolysis, and nonsense-mediated decay.
eRF3a and eRF3b isoform differences guide mammalian termination-complex and readthrough experiments.
eRF3a degraders support CFTR nonsense mutation rescue and premature stop codon readthrough studies.
- [1]. Song H, et al. The crystal structure of human eukaryotic release factor eRF1--mechanism of stop codon recognition and peptidyl-tRNA hydrolysis. Cell. 2000;100(3):311-321. [Content Brief]
- [2]. Alkalaeva EZ, et al. In vitro reconstitution of eukaryotic translation reveals cooperativity between release factors eRF1 and eRF3. Cell. 2006;125(6):1125-1136. [Content Brief]
- [3]. Cheng Z, et al. Structural insights into eRF3 and stop codon recognition by eRF1. Genes Dev. 2009;23(9):1106-1118. [Content Brief]
- [4]. Kashima I, et al. Binding of a novel SMG-1-Upf1-eRF1-eRF3 complex (SURF) to the exon junction complex triggers Upf1 phosphorylation and nonsense-mediated mRNA decay. Genes Dev. 2006;20(3):355-367. [Content Brief]
- [5]. Baradaran-Heravi A, et al. Effect of small molecule eRF3 degraders on premature termination codon readthrough. Nucleic Acids Res. 2021;49(7):3692-3708. [Content Brief]
- [6]. Chauvin C, et al. Involvement of human release factors eRF3a and eRF3b in translation termination and regulation of the termination complex formation. Mol Cell Biol. 2005;25(14):5801-5811. [Content Brief]
- [7]. Lee RE, et al. Small-molecule eRF3a degraders rescue CFTR nonsense mutations by promoting premature termination codon readthrough. J Clin Invest. 2022;132(18):e154571. [Content Brief]
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Eukaryotic Release Factor (eRF) Produits associés (3)
Produits associés (3)
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DP-15
0 ImagesDP-15 is a BRD4 and GSPT1 PROTAC degrader with DC50 values of 0.48 nM and 5.25 nM, respectively. DP-15 induces ubiquitination and degradation of BRD4 and GSPT1. DP-15 induces Apoptosis. DP-15 exerts anticancer activity against acute myeloid leukemia and non-Hodgkin's lymphoma cells. DP-15 can be used in studies related to acute myeloid leukemia and non-Hodgkin's lymphoma.
