ATPase-dependent role of the atypical kinase Rio2 on the evolving pre-40S ribosomal subunit

Ferreira-Cerca, Sébastien; Sagar, Vatsala; Schäfer, Thorsten; Diop, Momar Coumba; Wesseling, Anne-Maria; Lu, H. Y.; Chai, Eileen; Hurt, Ed; LaRonde-LeBlanc, N.

doi:10.1038/nsmb.2403

Cited by 121 publications

(256 citation statements)

References 39 publications

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“…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). It has been speculated that the ATPase activity of RIO2 could drive structural changes in pre-40S particles to promote their cytoplasmic maturation (Zemp et al, 2009;Ferreira-Cerca et al, 2012).…”

Section: Introductionmentioning

confidence: 51%

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: Introductionmentioning

confidence: 51%

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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“…First, formation of the characteristic beak structure involves the stable incorporation of uS3, which is triggered by the phosphorylation-dependent release of Ltv1 [22,75,76] (Figure 2G). The Rio2 ATPase is strategically positioned between the body and the maturing head in proximity to the decoding center and subsequently may act as a self-releasing checkpoint factor [73,77]. Recruitment of the ATPase Rio1, presumably requiring the prior dissociation of Tsr1 [78], yields late pre-40S ribosomes that are competent to join 60S subunits [79][80][81].…”

Section: Final Maturation Of Pre-40s Particlesmentioning

confidence: 99%

A Puzzle of Life: Crafting Ribosomal Subunits

Kressler

Hurt

Baßler

2017

Trends in Biochemical Sciences

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The biogenesis of eukaryotic ribosomes is a complicated process during which the transcription, modification, folding, and processing of the rRNA is coupled with the ordered assembly of $80 ribosomal proteins (r-proteins). Ribosome synthesis is catalyzed and coordinated by more than 200 biogenesis factors as the preribosomal subunits acquire maturity on their path from the nucleolus to the cytoplasm. Several biogenesis factors also interconnect the progression of ribosome assembly with quality control of important domains, ensuring that only functional subunits engage in translation. With the recent visualization of several assembly intermediates by cryoelectron microscopy (cryo-EM), a structural view of ribosome assembly begins to emerge. In this review we integrate these first structural insights into an updated overview of the consecutive ribosome assembly steps. Synopsis of Eukaryotic Ribosome AssemblyRibosomes are the molecular machines that translate the genetic information from the intermediary mRNA templates into proteins [1]. Eukaryotic 80S ribosomes comprise two unequal subunits that contain four different rRNAs and around 80 r-proteins ( Figure 1). The small 40S subunit (SSU) comprises the 18S rRNA and 33 r-proteins (referred to as RPS or S). The large 60S subunit (LSU) comprises the 25S/28S, 5.8S, and 5S rRNA and, in most eukaryotic species, 47 r-proteins (RPL or L); a notable exception is budding yeasts, which lack eL28The act of building a ribosome begins in the nucleolus, where the ribosomal DNA (rDNA) is transcribed into a long pre-rRNA precursor (35S pre-rRNA in yeast) and involves the ordered assembly of the r-proteins with the pre-rRNA, which is concomitantly processed into the mature rRNA species [5][6][7][8] (Figure 1 and Box 1). These assembly and processing events are tightly coupled and occur within preribosomal particles (see Glossary) that travel, as maturation progresses, from the nucleus across nuclear pore complexes (NPCs) to the cytoplasm, where they are ultimately converted into translation-competent ribosomal subunits [5,[9][10][11][12][13] (Figure 2, Key Figure). Given the gargantuan complexity of this process, it is unsurprising that the assembly of eukaryotic ribosomes strictly requires the assistance of a plethora (>200) of mostly essential ribosome biogenesis factors, which are also called trans-acting or assembly factors [5,14,15].Our current knowledge has been mainly obtained by studying ribosome biogenesis in the yeast Saccharomyces cerevisiae. Research conducted in the 1970s defined the r-protein composition of ribosomes, revealed the major pre-rRNA processing intermediates, and uncovered the existence of the 90S, 43S, and 66S preribosomal particles. The following 25 years witnessed the identification of numerous biogenesis factors and attributed functional roles TrendsCryoelectron microscopy analyses of the 90S preribosome show that the biogenesis factors create a casting mold that encloses the nascent pre-40S subunit.Structures of nuclear pre-60S particles reveal that a...

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“…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 .…”

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confidence: 99%

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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ATPase-dependent role of the atypical kinase Rio2 on the evolving pre-40S ribosomal subunit

Cited by 121 publications

References 39 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

A Puzzle of Life: Crafting Ribosomal Subunits

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

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