The kinase activity of human Rio1 is required for final steps of cytoplasmic maturation of 40S subunits

Widmann, Barbara; Wandrey, Franziska; Badertscher, Lukas; Wyler, Emanuel; Pfannstiel, Jens; Zemp, Ivo; Kutay, Ulrike

doi:10.1091/mbc.e11-07-0639

Cited by 98 publications

(154 citation statements)

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“…Several protein kinases associate with, and contribute to, the maturation of late 40S precursors (Rouquette et al, 2005;Zemp et al, 2009;Baumas et al, 2012;Widmann et al, 2012; this study), indicating a prominent role for phosphorylation in this process. The substrates of RIO family members have not been identified to date, and for RIO2 it has even been proposed that its ATPase activity mediates a conformational switch, rather than phosphorylation (Ferreira-Cerca et al, 2012).…”

Section: Discussionmentioning

confidence: 57%

“…Recent data demonstrate that the human protein kinases RIO1, RIO2 and RIO3 are components of pre-40S particles and are required for their cytoplasmic maturation (Rouquette et al, 2005;Zemp et al, 2009;Baumas et al, 2012;Widmann et al, 2012). Although phosphorylation substrates for RIO kinases have not been found, recycling of certain 40S transacting factors and pre-rRNA processing are dependent on the kinase/ATPase activity of the RIO kinases (Zemp et al, 2009;Widmann et al, 2012). Recent structural and biochemical analysis of RIO2 from the lower eukaryote Chaetomium thermophilum confirmed this conclusion (Ferreira-Cerca et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

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CK1δ and CK1ε are components of human 40S subunit precursors required for cytoplasmic 40S maturation

Zemp

Wandrey

Rao

et al. 2014

Journal of Cell Science

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Biogenesis of 40S pre-ribosomal subunits requires many transacting factors, among them several protein kinases. In this study, we show that the human casein kinase 1 (CK1) isoforms d and e are required for cytoplasmic maturation steps of 40S subunit precursors. We show that both CK1d and CK1e isoforms are components of pre-40S subunits, on which they phosphorylate the ribosome biogenesis factors ENP1/BYSL and LTV1. Inhibition or codepletion of CK1d and CK1e results in failure to recycle a series of trans-acting factors including ENP1/BYSL, LTV1, RRP12, DIM2/ PNO1, RIO2 and NOB1 from pre-40S particles after nuclear export. Furthermore, co-depletion of CK1d and CK1e leads to defects in 18S-E pre-rRNA processing. Together, these data demonstrate that CK1d and CK1e play a decisive role in triggering late steps of pre-40S maturation that are required for acquisition of functionality of 40S ribosomal subunits in protein translation.

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Section: Discussionmentioning

confidence: 57%

Section: Introductionmentioning

confidence: 99%

CK1δ and CK1ε are components of human 40S subunit precursors required for cytoplasmic 40S maturation

Zemp

Wandrey

Rao

et al. 2014

Journal of Cell Science

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“…Rio1 and its human orthologue RIOK1 promote the endonucleolytic cleavage of 20S pre-rRNA at pre-40S ribosomes, and stimulate the recycling of trans-acting factors that catalyse 40S maturation 12,[18][19][20] . While these events occur in the cytoplasm, a small pool of RIOK1 also localizes to the human nucleus 19,20 .…”

Section: Discussionmentioning

confidence: 99%

“…While these events occur in the cytoplasm, a small pool of RIOK1 also localizes to the human nucleus 19,20 . Treating murine cells with toyocamycin, an inhibitor of Rio1 activity in vitro 61 , impeded nucleolar pre-rRNA processing 62 , indicating that RIOK1 might be involved in early pre-rRNA cleavage, as we observed for Rio1 in yeast.…”

Section: Discussionmentioning

confidence: 99%

“…Noteworthy, the RIO kinases may act especially as ATPases as they exhibit o0.1% kinase activity in vitro [12][13][14] . Cytoplasmic Rio1 contributes to pre-40S ribosome biogenesis by promoting 20S pre-rRNA maturation and by stimulating the recycling of trans-acting factors at the pre-40S subunit, both in yeast 12,[15][16][17][18] and human cells 19,20 . Roles in the nucleus are unknown for any RIO member, either in yeast or eukaryotes beyond.…”

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Rio1 promotes rDNA stability and downregulates RNA polymerase I to ensure rDNA segregation

et al. 2015

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The conserved protein kinase Rio1 localizes to the cytoplasm and nucleus of eukaryotic cells. While the roles of Rio1 in the cytoplasm are well characterized, its nuclear function remains unknown. Here we show that nuclear Rio1 promotes rDNA array stability and segregation in Saccharomyces cerevisiae. During rDNA replication in S phase, Rio1 downregulates RNA polymerase I (PolI) and recruits the histone deacetylase Sir2. Both interventions ensure rDNA copy-number homeostasis and prevent the formation of extrachromosomal rDNA circles, which are linked to accelerated ageing in yeast. During anaphase, Rio1 downregulates PolI by targeting its subunit Rpa43, causing PolI to dissociate from the rDNA. By stimulating the processing of PolI-generated transcripts at the rDNA, Rio1 allows for rDNA condensation and segregation in late anaphase. These events finalize the genome transmission process. We identify Rio1 as an essential nucleolar housekeeper that integrates rDNA replication and segregation with ribosome biogenesis. A t anaphase onset, the replicated chromosomes separate and then segregate along the mitotic spindle into the daughter cells. In the budding yeast Saccharomyces cerevisiae, the locus containing the genes that encode the ribosomal RNAs (rDNA) segregates after the rest of the genome, in late anaphase [1][2][3][4] . The rDNA locus exists as a tandem-repeat array comprising B150 rDNA units containing the 35S and 5S genes, which are transcribed by RNA polymerase I (PolI) and PolIII, respectively. Processing of the 35S pre-rRNA generates 5.8S, 18S and 25S rRNA that, together with the 5S rRNA, become the catalytic backbones of each ribosome 5,6 . Only in anaphase does yeast repress rDNA transcription 4 , which allows the sister rDNA loci to condensate and segregate. PolI downregulation in anaphase is mediated by the Cdc14 phosphatase acting on PolI subunit Rpa43 (ref. 4), resulting in PolI dissociating from the 35S rDNA. The removal of PolI and the local resolution of its transcripts allow the condensin complex to bind. The latter compacts the rDNA array and recruits the DNA decatenating enzyme topoisomerase II (refs 1,3,4,7) resulting in the physical separation and subsequent segregation of the sister rDNA loci.S. cerevisiae Rio1 belongs to the atypical RIO protein kinase family whose members lack the activation loop and substrate recognition domain present in canonical eukaryotic protein kinases [8][9][10][11] . Noteworthy, the RIO kinases may act especially as ATPases as they exhibit o0.1% kinase activity in vitro [12][13][14] . Cytoplasmic Rio1 contributes to pre-40S ribosome biogenesis by promoting 20S pre-rRNA maturation and by stimulating the recycling of trans-acting factors at the pre-40S subunit, both in yeast 12,[15][16][17][18] and human cells 19,20 . Roles in the nucleus are unknown for any RIO member, either in yeast or eukaryotes beyond. Using S. cerevisiae, we now describe the first activities of Rio1 in the nucleus. Foremost, Rio1 downregulates PolI transcription through the cell cycle. In G...

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Comparison of preribosomal RNA processing pathways in yeast, plant and human cells – focus on coordinated action of endo‐ and exoribonucleases

2017

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Edited by Michael IbbaProper regulation of ribosome biosynthesis is mandatory for cellular adaptation, growth and proliferation. Ribosome biogenesis is the most energetically demanding cellular process, which requires tight control. Abnormalities in ribosome production have severe consequences, including developmental defects in plants and genetic diseases (ribosomopathies) in humans. One of the processes occurring during eukaryotic ribosome biogenesis is processing of the ribosomal RNA precursor molecule (pre-rRNA), synthesized by RNA polymerase I, into mature rRNAs. It must not only be accurate but must also be precisely coordinated with other phenomena leading to the synthesis of functional ribosomes: RNA modification, RNA folding, assembly with ribosomal proteins and nucleocytoplasmic RNP export. A multitude of ribosome biogenesis factors ensure that these events take place in a correct temporal order. Among them are endo-and exoribonucleases involved in pre-rRNA processing. Here, we thoroughly present a wide spectrum of ribonucleases participating in rRNA maturation, focusing on their biochemical properties, regulatory mechanisms and substrate specificity. We also discuss cooperation between various ribonucleolytic activities in particular stages of pre-rRNA processing, delineating major similarities and differences between three representative groups of eukaryotes: yeast, plants and humans.Keywords: endoribonuclease; exoribonuclease; pre-rRNA processing; ribosome biogenesis; RNA quality control; RNA trimming Ribosome biosynthesis is a multistep process that includes several tightly controlled events -ribosomal DNA (rDNA) transcription, processing of rRNA precursors into mature molecules, accompanied by binding of ribosome biogenesis factors (RBFs) and ribosomal proteins (RPs), and the final assembly of all Abbreviations CD, catalytic domain; dsRBD, double-stranded RNA-binding domain; ETS, external transcribed spacer; ITS, internal transcribed spacer; LSU, large ribosome subunit (60S); miRNA, microRNA; mRNA, messenger RNA; MRP RNA, noncoding RNA component of the RNase MRP; mTOR, mammalian target of rapamycin; nt(s), nucleotide(s); PIN domain, PilT N-terminal domain; Pol I/II/III, RNA polymerase I/II/III; prerRNA, ribosomal RNA precursor; RBF, ribosome biogenesis factor; RMRP, RNase MRP (mitochondrial RNA processing ribonuclease); RNase, ribonuclease; RNB domain, RNase II domain; RNP, ribonucleoprotein; RP, ribosomal protein; rRNA, ribosomal RNA; siRNA, short interfering RNA; snoRNA, small nucleolar RNA; snoRNP, small nucleolar ribonucleoprotein; snRNA, small nuclear RNA; SSU, small ribosome subunit (40S); TRAMP4 or TRAMP5, Trf4/Air/Mtr4 or Trf5/Air/Mtr4 polyadenylation complex; tRNA, transfer RNA.

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The kinase activity of human Rio1 is required for final steps of cytoplasmic maturation of 40S subunits

Cited by 98 publications

References 32 publications

CK1δ and CK1ε are components of human 40S subunit precursors required for cytoplasmic 40S maturation

CK1δ and CK1ε are components of human 40S subunit precursors required for cytoplasmic 40S maturation

Rio1 promotes rDNA stability and downregulates RNA polymerase I to ensure rDNA segregation

Comparison of preribosomal RNA processing pathways in yeast, plant and human cells – focus on coordinated action of endo‐ and exoribonucleases

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