The eIF3c/NIP1 PCI domain interacts with RNA and RACK1/ASC1 and promotes assembly of translation preinitiation complexes
Year: 2011
Type: article
Abstract: Several subunits of the multifunctional eukaryotic translation initiation factor 3 (eIF3) contain well-defined domains. Among them is the conserved bipartite PCI domain, typically serving as the principal scaffold for multisubunit 26S proteasome lid, CSN and eIF3 complexes, which constitutes most of the C-terminal region of the c/NIP1 subunit. Interestingly, the c/NIP1-PCI domain is exceptional in that its deletion, despite being lethal, does not affect eIF3 integrity. Here, we show that a short C-terminal truncation and two clustered mutations directly disturbing the PCI domain produce lethal or slow growth phenotypes and significantly reduce amounts of 40S-bound eIF3 and eIF5 in vivo. The extreme C-terminus directly interacts with blades 1-3 of the small ribosomal protein RACK1/ASC1, which is a part of the 40S head, and, consistently, deletion of the ASC1 coding region likewise affects eIF3 association with ribosomes. The PCI domain per se shows strong but unspecific binding to RNA, for the first time implicating this typical protein-protein binding domain in mediating protein-RNA interactions also. Importantly, as our clustered mutations severely reduce RNA binding, we conclude that the c/NIP1 C-terminal region forms an important intermolecular bridge between eIF3 and the 40S head region by contacting RACK1/ASC1 and most probably 18S rRNA.
Source: Nucleic Acids Research
DOI: 10.1093/nar/gkr1083
Institution: Czech Academy of Sciences, Institute of Microbiology
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,992
Funder: Wellcome Trust
Awards: Understanding the multiple roles of the key eukaryotic translation initiation factor 3 (eIF3) and its associated eIFs in both general and gene-specific translational control on the molecular level, In depth analysis of the interactions between the Multifactor Complex (MFC) composed of elFs 1, 3, 5 and elF2-GTP-Met-tRNAiMet and the 40S ribosomal subunit and their physiological importance for the regulation of eukaryotic, Understanding the multiple roles of the key eukaryotic translation initiation factor 3 (eIF3) and its associated eIFs in both general and gene-specific translational control on the molecular level.
OpenAlex ID: W2134860105