Abstract
BackgroundPCI/MPN domain protein complexes comprise the 19S proteasome lid, the COP9 signalosome (CSN), and eukaryotic translation initiation factor 3 (eIF3). The eIF3 complex is thought to be composed of essential core subunits required for global protein synthesis and non-essential subunits that may modulate mRNA specificity. Interactions of unclear significance were reported between eIF3 subunits and PCI proteins contained in the CSN.ResultsHere, 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.ConclusionWe propose that the PCI proteins eIF3e and eIF3m define distinct eIF3 complexes that may assist in the translation of different sets of mRNAs.
Highlights
PCI/MPN domain protein complexes comprise the 19S proteasome lid, the COP9 signalosome (CSN), and eukaryotic translation initiation factor 3
Three protein complexes that are conserved from yeast to humans, the 19S proteasome lid, the CSN, and eukaryotic translation initiation factor 3 (eIF3), contain subunits characterized by two protein motifs: the MPN (Mpr1/ Pad1 N-terminal) and the PCI
Our study provides the first experimental evidence substantiating this hypothesis by demonstrating that biochemically distinct eIF3 complexes defined by the PCI domain proteins eIF3e and eIF3m associate with different sets of mRNAs
Summary
PCI/MPN domain protein complexes comprise the 19S proteasome lid, the COP9 signalosome (CSN), and eukaryotic translation initiation factor 3 (eIF3). CSN promotes the activity of cullin-RING ubiquitin ligases [10,11,12,13,14,15,16], multiprotein complexes containing cullins, the RING protein RBX1, and one of several hundred substrate-specific adaptors [17,18,19,20,21,22]. The MPN domain containing CSN subunit 5 harbors a protease motif [23] that cleaves the ubiquitin-related peptide NEDD8 from cullins [24,25]. This activity, acting in concert with the CSN-associated deubiquitylation enzyme Ubp, was proposed to promote cullin function by facilitating the recruitment of labile substrate adaptors [11,16,26,27]
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