Distinct genome protective vs. ribosome synthetic functions of the paralogous nucleolar proteins nucleostemin and GNL3L

The mammalian nucleolar proteins nucleostemin (NS) and GNL3L (for GNL3-like) are encoded by paralogous genes that arose from an invertebrate ancestral gene, GNL3. Invertebrate GNL3 has been implicated in ribosome biosynthesis as has its mammalian descendent GNL3L, whereas the paralogous mammalian NS...

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Veröffentlicht in:Journal of cell science 2014-01
Hauptverfasser: Lin, Tao, Meng, Lingjun, Lin, Tsung-Chin, Wu, Laura J., Pederson, Thoru, Tsai, Robert Y. L.
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Sprache:eng
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Zusammenfassung:The mammalian nucleolar proteins nucleostemin (NS) and GNL3L (for GNL3-like) are encoded by paralogous genes that arose from an invertebrate ancestral gene, GNL3. Invertebrate GNL3 has been implicated in ribosome biosynthesis as has its mammalian descendent GNL3L, whereas the paralogous mammalian NS gene has instead been implicated in cell renewal. Here we found that NS depletion in a human breast carcinoma cell line triggered a prompt and significant effect of DNA damage in S-phase cells without perturbing the initial step of rRNA synthesis and only mildly affected the total ribosome production. In contrast, GNL3L depletion markedly impaired ribosome production without inducing appreciable DNA damage. These results indicate that during vertebrate evolution GNL3L retained the role of the ancestral gene in ribosome biosynthesis while the paralogous NS acquired a novel genome-protective function. Our results provide a coherent explanation for what had seemed to be contradictory findings about the functions of the invertebrate vs. vertebrate genes, and also speak to how the nucleolus was fine-tuned for a role in genome protection and cell cycle control as the vertebrates evolved.
ISSN:0021-9533
1477-9137
DOI:10.1242/jcs.143842