Characterization of the Ribosomal Stress Response Pathway Leading to Cell Cycle Arrest in Arabidopsis thaliana

When ribosome biogenesis or function is perturbed, plant cells undergo ribosomal stress, leading to growth defects and developmental alterations. The plant ribosomal stress response has recently gained recognition, but its molecular mechanism remains elusive. Here, we characterized this response in Arabidopsis thaliana using ribosome biogenesis-impairing mutations (rid2 and rid3) and ribosome biogenesis/function-interfering drugs (5-fluorouracil and puromycin) as ribosomal stressors. These stressors repressed cell proliferation and increased ploidy levels indicative of endoreduplication. Under the ribosomal stress conditions, a subset of NAC transcription factor genes and CDK inhibitor genes were upregulated, while they tended to downregulate G2/M-specific genes. Overexpression of ANAC082, which encodes a NAC factor implicated in the ribosomal stress response pathway, phenocopied the ribosomal stress response in the cellular behavior and gene expression. These results together indicated that, predominantly mediated by ANAC082, ribosomal stress arrests the cell cycle at G2 and promotes endoreduplication. Comparison of gene expressions and genetic relations between the ribosomal and DNA damage stress responses, focusing on ANAC082 and the DNA damage stress response-mediating NAC factor SOG1, revealed that these stress response pathways are distinct and largely independent from each other, although they have similar outputs in the control of cell proliferation and endoreduplication.