Ribosome biogenesis plays key roles in cell growth by providing increased capacity for protein synthesis. It requires coordinated production of ribosomal proteins (RP) and ribosomal RNA (rRNA), including the processing of the latter. Here, we show that, the depletion of RPS19 causes a reduction of rRNA synthesis in cell lines of both erythroid and non-erythroid origin. A similar effect is observed upon depletion of RPS6 or RPL11. The deficiency of RPS19 does not alter the stability of rRNA, but instead leads to an inhibition of RNA Polymerase I (Pol I) activity. In fact, results of nuclear run-on assays and ChIP experiments show that association of Pol I with the rRNA gene is reduced in RPS19-depleted cells. The phosphorylation of three known regulators of Pol I, CDK2, AKT and AMPK, is altered during ribosomal stress and could be involved in the observed downregulation. Finally, RNA from patients with Diamond Blackfan Anemia (DBA), shows, on average, a lower level of 47S precursor. This indicates that inhibition of rRNA synthesis could be one of the molecular alterations at the basis of DBA.

Juli, G., Gismondi, A., Monteleone, V., Caldarola, S., Iadevaia, V., Aspesi, A., et al. (2016). Depletion of ribosomal protein S19 causes a reduction of rRNA synthesis. SCIENTIFIC REPORTS, 6, 35026 [10.1038/srep35026].

Depletion of ribosomal protein S19 causes a reduction of rRNA synthesis

JULI, GIADA;GISMONDI, ANGELO;MONTELEONE, VALENTINA;CALDAROLA, SARA;IADEVAIA, VALENTINA;LORENI, FABRIZIO
2016

Abstract

Ribosome biogenesis plays key roles in cell growth by providing increased capacity for protein synthesis. It requires coordinated production of ribosomal proteins (RP) and ribosomal RNA (rRNA), including the processing of the latter. Here, we show that, the depletion of RPS19 causes a reduction of rRNA synthesis in cell lines of both erythroid and non-erythroid origin. A similar effect is observed upon depletion of RPS6 or RPL11. The deficiency of RPS19 does not alter the stability of rRNA, but instead leads to an inhibition of RNA Polymerase I (Pol I) activity. In fact, results of nuclear run-on assays and ChIP experiments show that association of Pol I with the rRNA gene is reduced in RPS19-depleted cells. The phosphorylation of three known regulators of Pol I, CDK2, AKT and AMPK, is altered during ribosomal stress and could be involved in the observed downregulation. Finally, RNA from patients with Diamond Blackfan Anemia (DBA), shows, on average, a lower level of 47S precursor. This indicates that inhibition of rRNA synthesis could be one of the molecular alterations at the basis of DBA.
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Rilevanza internazionale
Articolo
Esperti anonimi
Settore BIO/11
English
Con Impact Factor ISI
Juli, G., Gismondi, A., Monteleone, V., Caldarola, S., Iadevaia, V., Aspesi, A., et al. (2016). Depletion of ribosomal protein S19 causes a reduction of rRNA synthesis. SCIENTIFIC REPORTS, 6, 35026 [10.1038/srep35026].
Juli, G; Gismondi, A; Monteleone, V; Caldarola, S; Iadevaia, V; Aspesi, A; Dianzani, I; Proud, C; Loreni, F
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/172897
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