Work

Eukaryotic initiation factor eIF3 facilitates loading of eukaryotic release factor eRF1 or suppressor tRNA to the ribosome

Year: 2025

Type: article

Abstract: Eukaryotic translation initiation factor eIF3 plays a pivotal role in 48S preinitiation complex assembly and ribosomal scanning. It binds simultaneously to the 40S ribosomal subunit and the eIF4F cap-binding complex, which, through its interaction with poly(A)-binding protein (PABP), facilitates closed-loop mRNA structure formation. PABP also interacts with the eukaryotic release factor eRF3, thereby co-localizing initiation and release factors, and suggesting potential functional crosstalk. Using a reconstituted mammalian translation system, we demonstrate that eIF3 significantly enhances translation termination. Specifically, eIF3 promotes the loading of eRF1 into the ribosomal A site, accelerating the GTPase activity of eRF3 and the rate of peptide release. We also show that eIF3 facilitates the binding of suppressor or near-cognate tRNAs to stop codons to enable readthrough and continued elongation. These findings establish a conserved, direct role of eIF3 in regulation both translation termination and stop codon readthrough, a mechanism particularly relevant within closed-loop mRNA structures and during upstream open reading frame translation.

Source: Nucleic Acids Research

DOI: 10.1093/nar/gkaf1372

Authors: Ekaterina Shuvalova, Alexey Shuvalov, Walaa Al Sheikh, Alexandr Klishin, Nikita Biziaev, Elena Alkalaeva

Institutions: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences

Language: English

Topic: RNA and protein synthesis mechanisms

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: gold

Estimated APC paid: $3,992

Funder: Russian Science Foundation