The Evolution of COP9 Signalosome in Unicellular and Multicellular Organisms

Abstract

The COP9 signalosome (CSN) is a highly conserved protein complex, recently being crystallized for human. In mammals and plants the COP9 complex consists of nine subunits, CSN 1–8 and CSNAP. The CSN regulates the activity of culling ring E3 ubiquitin and plays central roles in pleiotropy, cell cycle, and defense of pathogens. Despite the interesting and essential functions, a thorough analysis of the CSN subunits in evolutionary comparative perspective is missing. Here we compared 61 eukaryotic genomes including plants, animals, and yeasts genomes and show that the most conserved subunits of eukaryotes among the nine subunits are CSN2 and CSN5. This may indicate a strong evolutionary selection for these two subunits. Despite the strong conservation of the protein sequence, the genomic structures of the intron/exon boundaries indicate no conservation at genomic level. This suggests that the gene structure is exposed to a much less selection compared with the protein sequence. We also show the conservation of important active domains, such as PCI (proteasome lid-CSN-initiation factor) and MPN (MPR1/PAD1 amino-terminal). We identified novel exons and alternative splicing variants for all CSN subunits. This indicates another level of complexity of the CSN. Notably, most COP9-subunits were identified in all multicellular and unicellular eukaryotic organisms analyzed, but not in prokaryotes or archaeas. Thus, genes encoding CSN subunits present in all analyzed eukaryotes indicate the invention of the signalosome at the root of eukaryotes. The identification of alternative splice variants indicates possible “mini-complexes” or COP9 complexes with independent subunits containing potentially novel and not yet identified functions.

Meloidogyne incognita PASSE-MURAILLE (MiPM) Gene Encodes a Cell-Penetrating Protein That Interacts With the CSN5 Subunit of the COP9 Signalosome

“…As previously mentioned, CSN5 has been extensively described as a central regulator of the CSN complex (Chamovitz and Segal, 2001 ; Barth et al, 2016 ). It is worthy to note that we successfully identified all of eight tobacco CSN subunits (Figure 1C , Table S1 ).…”

“…Among the hub candidates identified in Arabidopsis, the isoform CSN5a protein (also known as Jab1 or COPS5) is the most targeted host hub protein that interacts with at least 30 effectors secreted by various phytopathogens (Lozano-Duran et al, 2011 ; Mukhtar et al, 2011 ; Weßling et al, 2014 ). CSN5 is approximately 40 kDa protein and is highly conserved across kingdoms, which shares ~60% amino acid sequence identity between plants and animals (Barth et al, 2016 ). CSN5 is one of the eight subunits of the CSN complex, highly conserved amongst eukaryotes (Chamovitz and Segal, 2001 ; Barth et al, 2016 ).…”

“…CSN5 is approximately 40 kDa protein and is highly conserved across kingdoms, which shares ~60% amino acid sequence identity between plants and animals (Barth et al, 2016 ). CSN5 is one of the eight subunits of the CSN complex, highly conserved amongst eukaryotes (Chamovitz and Segal, 2001 ; Barth et al, 2016 ). The CSN complex was first described in Arabidopsis as a photomorphogenic regulator of light-controlled plant growth and development (Wei et al, 1994 ; Chamovitz and Segal, 2001 ).…”

Rub1/NEDD8, a ubiquitin-like modifier, is also a ubiquitin modifier

“…The paucity of Rub1 targets and the divergence of Rub1 and Ub cellular landscapes are puzzling, given that the two proteins share ~60% sequence identity, an identical tertiary fold (16), and key recognition elements on their surface (Fig 1 A-C). We note that genes encoding for Ub and Rub1 are found in all eukaryotes (17,18), although conservation of Ub is far greater than that of Rub1 orthologs (Fig 1B). Accordingly, throughout this text we retain the species-specific nomenclature for RUB1/NEDD8 unless addressing general properties of the proteins, in which case we will refer to "Rub1".…”

The Role of Selective Protein Degradation in the Regulation of Iron and Sulfur Homeostasis in Plants

“…The COP9 signalosome (CSN) is an eight-subunit complex that regulates the activity of CULLIN-RING E3 ubiquitin ligases (CRLs) [89]. Recently, CSN has been proven to regulate the proteasome-mediated degradation of iron deficiency-inducible transcription factor, IDEF1, in rice [90].…”