Plant Deubiquitinases and Their Role in the Control of Gene Expression Through Modification of Histones

Abstract

Selective degradation of proteins in the cell occurs through ubiquitination, which consists of post-translational deposition of ubiquitin on proteins to target them for degradation by proteases. However, ubiquitination does not only impact on protein stability, but promotes changes in their functions. Whereas the deposition of ubiquitin has been amply studied and discussed, the antagonistic activity, deubiquitination, is just emerging and the full model and players involved in this mechanism are far from being completely understood. Nevertheless, it is the dynamic balance between ubiquitination and deubiquitination that is essential for the development and homeostasis of organisms. In this review, we present a detailed analysis of the members of the deubiquitinase (DUB) superfamily in plants and its division in different clades. We describe current knowledge in the molecular and functional characterisation of DUB proteins, focusing primarily on Arabidopsis thaliana. In addition, the striking function of the duality between ubiquitination and deubiquitination in the control of gene expression through the modification of chromatin is discussed and, using the available information of the activities of the DUB superfamily in yeast and animals as scaffold, we propose possible scenarios for the role of these proteins in plants.

Keywords: Arabidopsis; chromatin; deubiquitination; epigenetics; gene expression; histone modifications; plant development; ubiquitin.

FIGURE 1

Ubiquitin-specific-processing proteases (UBPs) are highly conserved in plants. Arabidopsis lyrata (AL), Capsella rubella (CRU), Brassica rapa (BRO), Popolus trichocarpa (PT), Physcomitrella patens (PP). The analysis was conducted in Clustal Omega (Sievers et al., 2014). The tree was edited for easier visualization in MEGA 7. Sequences obtained from PLAZA (Proost et al., 2015).

FIGURE 2

Consensus phylogenetic tree of UBPs/USPs. The tree shows phylogenetic conservation of proteins from Arabidopsis, Drosophila, and humans. The analysis was conducted in MEGA7 (Kumar et al., 2016). The tree was constructed by the Neighbor-Joining method with bootstrap resampling (5000 replicates). The numbers in the nodes indicate bootstrap values. The distances were computed using the Poisson method. Scale bars indicate units of the number of amino acid substitutions per site.

FIGURE 3

Arabidopsis UCH family and the high sequence similarity proteins in Humans and Drosophila. Phylogenetic analysis showing the 3 members of the UCH family based on protein sequence percentage of similarity and their domains. The analysis was conducted in MEGA7 (Kumar et al., 2016). The tree was constructed by the Neighbor-Joining method with bootstrap resampling (5000 replicates). The numbers in the nodes indicate bootstrap values. The distances were computed using the Poisson method. Scale bars indicate units of the number of amino acid substitutions per site. The numbers in the domain representation indicate the amino acids number.

FIGURE 4

Arabidopsis OTU family and the high sequence similarity proteins in Humans and Drosophila. Phylogenetic analysis showing the 12 members of the OUT family based on protein sequence percentage of similarity and their domains. The analysis was conducted in MEGA7 (Kumar et al., 2016). The tree was constructed by the Neighbor-Joining method with bootstrap resampling (5000 replicates). The numbers in the nodes indicate bootstrap values. The distances were computed using the Poisson method. Scale bars indicate units of the number of amino acid substitutions per site. The numbers in the domain representation indicate the amino acids number.

FIGURE 5

Arabidopsis Josephin family and the high sequence similarity proteins in Humans and Drosophila. Phylogenetic analysis showing the 2 members of the Josephin family based on protein sequence percentage of similarity and their domains. The analysis was conducted in MEGA7 (Kumar et al., 2016). The tree was constructed by the Neighbor-Joining method with bootstrap resampling (5000 replicates). The numbers in the nodes indicate bootstrap values. The distances were computed using the Poisson method. Scale bars indicate units of the number of amino acid substitutions per site. The numbers in the domain representation indicate the amino acids number.

FIGURE 6

Arabidopsis JAMM family and the high sequence similarity proteins in Humans and Drosophila. Phylogenetic analysis showing the 8 members of the JAMM family based on protein sequence percentage of similarity and their domains. The analysis was conducted in MEGA7 (Kumar et al., 2016). The tree was constructed by the Neighbor-Joining method with bootstrap resampling (5000 replicates). The numbers in the nodes indicate bootstrap values. The distances were computed using the Poisson method. Scale bars indicate units of the number of amino acid substitutions per site. The numbers in the domain representation indicate the amino acids number.

FIGURE 7

Schematic model showing the regulation of DUBs and support complexes involved in H2A and H2B monoubiquitination/deubiquitination. The figure represents four processes, H2A monoubiquitination, H2A deubiquitination, H2B monoubiquitination and H2B deubiquitination. Ubiquitin is represented by green circles. (A) H2A monoubiquitination. PRC1 function is conserved in Eukaryotes. In humans two additional USPs have been described in this process. (B) H2A deubiquitination. The role of PR-DUB has been describe in humans and flies, as well as three additional DUBs. The proteins involved in this process in Arabidopsis are still unveiled. (C) H2B monoubiquitination. Bre1 and two complexes (BUR-C and Paf1-C) are involved in the deposition of ubiquitin on the H2B. In Arabidopsis only the orthologues of Bre1 and his partner Rad6, have been described in relation to H2Bub1. (D) H2B deubiquitination. Several DUBs are involved in this process in different organisms. Arabidopsis has a SAGA-like complex but its role in H2B deubiquitination has not been demonstrated.