title: Depletion of ribosomal protein S19 causes a reduction of rRNA synthesis.
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.
authors.affiliation: Department of Biology, University of Rome Tor Vergata, Roma, Italy.
authors.forename: Giada
authors.initials: G
authors.lastname: Juli
authors.affiliation: Department of Biology, University of Rome Tor Vergata, Roma, Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: Gismondi
authors.affiliation: Department of Biology, University of Rome Tor Vergata, Roma, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Monteleone
authors.affiliation: Department of Biology, University of Rome Tor Vergata, Roma, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Caldarola
authors.affiliation: Centre for Biological Sciences, University of Southampton, Southampton, UK.
authors.forename: Valentina
authors.initials: V
authors.lastname: Iadevaia
authors.affiliation: Department of Health Sciences, Università del Piemonte Orientale, Novara, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Aspesi
authors.affiliation: Department of Health Sciences, Università del Piemonte Orientale, Novara, Italy.
authors.forename: Irma
authors.initials: I
authors.lastname: Dianzani
authors.affiliation: Centre for Biological Sciences, University of Southampton, Southampton, UK.
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Proud
authors.affiliation: Department of Biology, University of Rome Tor Vergata, Roma, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Loreni
mesh_terms: D000263:Adenylate Kinase / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D029503:Anemia, Diamond-Blackfan / Q000235:genetics*; D002460:Cell Line; D002648:Child; D002675:Child, Preschool; D051357:Cyclin-Dependent Kinase 2 / Q000378:metabolism; D005260:Female; D055786:Gene Knockout Techniques; D057809:HEK293 Cells; D006801:Humans; D020014:K562 Cells; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012318:RNA Polymerase I / Q000378:metabolism*; D020871:RNA Stability; D012335:RNA, Ribosomal / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D038601:Ribosomal Protein S6 / Q000235:genetics; D012269:Ribosomal Proteins / Q000235:genetics*; D055815:Young Adult
chemical_list: D012335:RNA, Ribosomal; C088179:RNA, ribosomal, 45S; D038601:Ribosomal Protein S6; D012269:Ribosomal Proteins; C027624:ribosomal protein L11; C040343:ribosomal protein S19; D051057:Proto-Oncogene Proteins c-akt; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D000263:Adenylate Kinase; D012318:RNA Polymerase I