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Several proteomic studies in Arabidopsis have shown the presence of heterogeneous ribosomal populations in different tissues. However, the phenotypic consequences of the imbalance of those ribosomal populations, and the regulatory mechanisms activated to control specific ratios between them, have yet to be evaluated. In our previous report, the phenotypic characterization of the ribosomal protein family L4 (RPL4) in Arabidopsis suggests that the maintenance of proper auxin-regulated developmental responses requires the simultaneous presence of RPL4A- and RPL4D-containing ribosomes. Based on the analysis of the compensatory mechanisms within the RPL4 family proteins in the rpl4a and rpl4d backgrounds, we propose the Gene Dosage Balance Hypothesis (GDBH) as a regulatory mechanism for ribosomal complexes in Arabidopsis. By using the concepts of dosage compensation and hierarchy, GDBH is able to explain the severity and specificity of different ribosomal mutant phenotypes associated with the same ribosomal complex.
The Arabidopsis ribosome is a complex structure whose assembly requires the proper temporal and spatial organization of four RNA species and 81 ribosomal proteins encoded by large multigene families.1,2 Although the presence of multigene families encoding ribosomal proteins suggests that the system maintains redundancy, several studies have shown that genetic defects in individual ribosomal components can cause deleterious developmental effects in a gene dosage dependent manner.3–6 Since the loss of a single Arabidopsis ribosomal protein affects the performance of the whole ribosomal complex, and this effect has been observed in different ribosomal protein mutants (RPMs),6 we questioned whether there is a common regulatory mechanism involving the different components of the ribosomal complex in Arabidopsis.
In yeast, the gene dosage effects of different elements belonging to protein complexes have been explained by a mechanistic model named the Gene Dosage Balance Hypothesis (GDBH).7 According to the GDBH, the stoichiometric rules that govern the assembly of proteins in a complex are essential for the function of the whole system and any deviation from the normal stoichiometry would be deleterious; thus, both underexpression and overexpression of individual components can potentially lower the fitness of the organism.7–11 The GDBH has been applied to different organisms and examples of complexes where underexpression of a single component is harmful include mutations in Drosophila melanogaster ribosomal genes that cause the Minute phenotype,12 and the quantitative reduction in synthesis of the human ribosomal protein S4 observed in individuals with Turner syndrome.13 Alternatively, examples of complexes where the overexpression of a single component has deleterious effects include the yeast genes GPA1, STE4 and STE18 which encode homologs of the mammalian G protein α, β and γ subunits respectively,14 and the Snf1/AMP-activated protein kinase complex involved in stress response.15 In this addendum we will discuss the application of the GDBH to the Arabidopsis ribosomal complexes and its consequences in the auxin-related phenotypes observed in different RPMs.
In Arabidopsis, different RPMs share impaired auxin-dependent responses but their phenotypic consequences differ in terms of severity.6 Instead of being considered quantitative traits, those phenotypic differences has been described as “specific” and widely used to sort and characterize each Arabidopsis RPM. Accordingly, the RPM stv1 has been characterized by its aberrant gynaeceum development,16 the RPMs rpl10a and rpl9 by their role in leaf patterning control,17 the RPMs rpl28a and rpl5a, by their role in leaf polarity,18 and the RPMs rpl4 by their vacuolar trafficking responses.6
From the regulatory point of view, the results from Rosado et al.6 support the GDBH as a plausible explanation for auxin-related phenotypes observed in different RPMs. In that study, the rpl4 mutations activate compensatory mechanisms that include the transcriptional and translational activation of the alternative ribosomal RPL4 family member. As a consequence, the amount of total RPL4 protein in different rpl4 mutant backgrounds is higher than in wild-type; however, the ratio of RPL4A:RPL4D in those backgrounds is imbalanced. Since the phenotypes found in our rpl4 imbalanced lines resemble several recessive RPMs,3,5,16–18 ribosomal silenced lines,19 and semi-dominant ribosomal mutations,20 we hypothesize that the phenotype specificity and severity of the different RPMs might be a consequence of a regulatory imbalance of the entire ribosomal complex as proposed by the GDBH (Fig. 1A–D). In this model, the outcome of deletions or duplications of genes encoding ribosomal components depends on their respective topological positions and mechanism of assembly into the complex.7,10 Thus, the independent spatial and temporal regulatory characteristics of each member of the r-protein families in Arabidopsis (Fig. 1E) as well as its hierarchical position within the ribosome might trigger specific compensatory mechanisms to cope with the absence of particular ribosomal proteins. Consequently, the severity and/or specificity of the auxin-related phenotypes in different RPMs described in the literature could be explained as the relative success of the remaining ribosomal proteins to coordinate their responses to assemble optimally functional ribosomes.
In conclusion, we postulate that GBDH is a regulatory mechanism that explains the severity and specificity of the auxin-related phenotypes observed in many Arabidopsis RPMs.
We thank Dr. Glenn Hicks (University of California, Riverside) for his critical reading of the manuscript. This work was funded by Department of Energy, Division of Energy Biosciences, Grant DE-FG03-02ER15295/A000.
Previously published online: www.landesbioscience.com/journals/psb/article/11341