2024年11月8日 · Eukaryotic initiation factor 4 A (eIF4A) plays critical roles during translation initiation of cellular mRNAs by forming the cap-binding eIF4F complex, recruiting...

Eukaryotic initiation factor 4A-III (eIF4A3), a core helicase component of the exon junction complex, is essential for splicing, mRNA trafficking, and nonsense-mediated decay processes emerging as targets in cancer therapy.

2019年2月19日 · Ryu et al. show that eIF4A3 (a core EJC component) is phosphorylated at the threonine 163 position by CDK1 and CDK2 in a cell cycle-dependent manner. This event triggers EJC remodeling and affects NMD efficiency in a cell cycle-dependent manner.

The overall topology of the human eIF4A-I/eIF4G/eIF4H complex has been dissected in a combination of NMR, mutational and binding studies. 53 Interactions were identified between the N-terminal RecA-like domain of eIF4A-I and the C-terminus of HEAT-1 in eIF4G, the C-terminal RecA-domain of eIF4A-I with HEAT-1, of both eIF4A-I domains with HEAT-2 ...

2017年7月21日 · No small molecules for NMD inhibition via selective inhibition of eIF4A3 have been discovered. Here, we identified allosteric eIF4A3 inhibitors from a high-throughput screening campaign. Chemical optimization of the lead compounds based on ATPase activity yielded compound 2, which exhibited noncompetitive inhibition with ATP or RNA and high ...

In this review, we explored the predicted structures of the three eIF4A isoforms (eIF4A1, eIF4A2, and eIF4A3), and discussed possible explanations for which function during different translation stages (initiation, mRNA localization, export, and mRNA splicing).

2021年11月19日 · Eukaryotic initiation factor 4A (eIF4A) proteins are essential for translation, exhibit bidirectional RNA helicase function, and act as RNA-dependent ATPases. In this review, we explored the predicted structures of the three eIF4A isoforms (eIF4A1, eIF4A2, and eIF4A3), and discussed possible explanations for which function during different ...

EIF4A3, a member of the DEAD-box protein family, is a nuclear matrix protein and a core component of the exon junction complex (EJC). Under physiological conditions, EIF4A3 participates in post-transcriptional gene regulation by promoting EJC control of precursor mRNA splicing, thus influencing nonsense-mediated mRNA decay.

2021年6月6日 · Here, we present the first crystal structure of an eIF4A1:RNA complex bound to an analogue of the marine sponge-derived natural product PatA, C5-desmethyl pateamine A (DMPatA). One end of this small molecule wedges itself between two RNA bases while the other end is cradled by several protein residues.

2025年2月2日 · Inhibition of eIF4A3 activity abolished UPF1 binding to NMD transcripts. Nonsense-Mediated mRNA Decay (NMD) is a key control mechanism of RNA quality widely described to target mRNA harbouring Premature Termination Codon (PTC). However, recent studies suggested the existence of non-canonical pathways which remain unresolved.