PCI proteins eIF3e and eIF3m define distinct translation initiation factor 3 complexes

Here, we report the unexpected finding that fission yeast has two distinct eIF3 complexes sharing common core subunits, but distinguished by the PCI proteins eIF3e and the novel eIF3m, which was previously annotated as a putative CSN subunit. Whereas neither eIF3e nor eIF3m contribute to the non-essential activities of CSN in cullin-RING ubiquitin ligase control, eif3m, unlike eif3e, is an essential gene required for global cellular protein synthesis and polysome formation. Using a ribonomic approach, this phenotypic distinction was correlated with a different set of mRNAs associated with the eIF3e and eIF3m complexes. Whereas the eIF3m complex appears to associate with the bulk of cellular mRNAs, the eIF3e complex associates with a far more restricted set. The microarray findings were independently corroborated for a random set of 14 mRNAs by RT-PCR analysis.We propose that the PCI proteins eIF3e and eIF3m define distinct eIF3 complexes that may assist in the translation of different sets of mRNAs.Three protein complexes that are conserved from yeast to humans, the 19S proteasome lid, the CSN, and eIF3, contain subunits characterized by two protein motifs: the MPN (Mpr1/ Pad1 N-terminal) and the PCI (proteasome/CSN/eIF3) domains [1]. The proteasome 20S catalytic particle and the 19S regulatory subunit cooperate in degrading polyubiquitylated proteins (reviewed in [2]). The 19S proteasome can be separated into the base complex, which binds and unfolds substrates [3], and the eight subunit lid complex, which cleaves ubiquitin from substrates, thus apparently facilitating the entry of substrates into the catalytic proteasome barrel [4,5].In higher eukaryotes, the subunits of the 19S lid show pair-wise similarity to the eight subunits of the CSN [6-9]. In vivo, CSN promotes the activity of cullin-RING ubiquitin ligases [10-16], multiprotein complexes containing cullins, the RING protein RBX1, and one of several hundred substrate-specific adaptors [17-22]. The MPN domai