A Molecular Titration System Coordinates Ribosomal Protein Gene Transcription with Ribosomal RNA Synthesis

Albert, Benjamin; Knight, Britta; Merwin, Jason R.; Martín, Victoria Sánchez; Ottoz, Diana S. M.; Gloor, Yvonne; Bruzzone, Maria Jessica; Rudner, Adam D.; Shore, David

doi:10.1016/j.molcel.2016.10.003

Cited by 55 publications

(100 citation statements)

References 38 publications

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“…While common promoter elements ensure the harmonized transcription of RPGs [34], a recent study revealed how a negative feedback loop links early assembly events with RPG transcription. A shortage of nascent pre-rRNAs leads to an increased free pool of the 90S biogenesis factor Utp22, which then sequesters the transcriptional activator Ifh1 from RPG promoters [35]. However, both the quantitative and qualitative production of r-proteins clearly depends also on several post-transcriptional events, including the stability and splicing efficiency of RPG mRNAs as well as the folding and intrinsic stability of r-proteins and, for most of these, their transport into the nucleus [6,36].…”

Section: Providing a Balanced Supply Of Ribosomal Componentsmentioning

confidence: 99%

A Puzzle of Life: Crafting Ribosomal Subunits

Kressler

Hurt

Baßler

2017

Trends in Biochemical Sciences

164

127

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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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Section: Providing a Balanced Supply Of Ribosomal Componentsmentioning

confidence: 99%

A Puzzle of Life: Crafting Ribosomal Subunits

Kressler

Hurt

Baßler

2017

Trends in Biochemical Sciences

164

127

View full text Add to dashboard Cite

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“…For example, Ifh1 is rapidly released from RP promoters only minutes following inhibition of the conserved eukaryotic growth regulator Target Of Rapamycin Complex 1 (TORC1) kinase (Schawalder et al, 2004). Although it has been shown that Ifh1 promoter binding is coordinated with RNA polymerase I (RNAPI) activity upon prolonged TORC1 inhibition to help balance RP and rRNA production (Albert et al, 2016;Rudra et al, 2007), how Ifh1 is removed from RP gene promoters to immediately down-regulate their expression following stress remains a mystery. Furthermore, possible links between RP gene expression, ribosomal assembly and the protein homeostasis transcription program driven by Hsf1 remain important open questions.…”

Section: Introductionmentioning

confidence: 99%

A ribosome assembly stress response regulates transcription to maintain proteome homeostasis

Albert¹,

Kos-Braun

Henras

et al. 2019

Preprint

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Ribosome biogenesis is a complex and energy-demanding process requiring tight coordination of ribosomal RNA (rRNA) and ribosomal protein (RP) production. Alteration of any step in this process may impact growth by leading to proteotoxic stress. Although the transcription factor Hsf1 has emerged as a central regulator of proteostasis, how its activity is coordinated with ribosome biogenesis is unknown. Here we show that arrest of ribosome biogenesis in the budding yeast S. cerevisiae triggers rapid activation of a highly specific stress pathway that coordinately up-regulates Hsf1 target genes and down-regulates RP genes. Activation of Hsf1 target genes requires neo-synthesis of RPs, which accumulate in an insoluble fraction, leading to sequestration of the RP transcriptional activator Ifh1.Our data suggest that levels of newly-synthetized RPs, imported into the nucleus but not yet assembled into ribosomes, work to continuously balance Hsf1 and Ifh1 activity, thus guarding against proteotoxic stress during ribosome assembly.

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“…Synthesis of ribosomes occupies considerable resources in all growing cells, which leads to a requirement for coordination between ribosomal protein synthesis and rRNA transcription. In mammalian cells and yeast, this coordination happens in the nucleus, at the level of transcription [17,18]. Trypanosomes also devote considerable resources to ribosome synthesis: in bloodstream-forms, resources devoted to rRNA transcription are at least as great as those needed for synthesis of mRNAs [19], and the ribosomal protein mRNAs together constitute more than 10% of total mRNA [20].…”

Section: Discussionmentioning

confidence: 99%

The endoplasmic reticulum-associated mRNA-binding proteins ERBP1 and ERBP2 interact in bloodstream-formTrypanosoma brucei

Bajak

Leiss

Clayton

et al. 2019

Preprint

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Kinetoplastids rely heavily on post-transcriptional mechanisms for control of gene expression, and on RNA-binding proteins that regulate mRNA splicing, translation and decay. Trypanosoma brucei ERBP1 (Tb927.10.14150) and ERBP2 (Tb927.9.9550) were previously identified as mRNA binding proteins that lack canonical RNA-binding domains. We here show that ERBP1 is associated with the endoplasmic reticulum, like ERBP2, and that the two proteins interact in vivo. Loss of ERBP1 from bloodstream-form T. brucei initially resulted in a growth defect but proliferation was restored after more prolonged cultivation. Results from a pull-down of tagged ERBP1 suggest that it preferentially binds to ribosomal protein mRNAs. The ERBP1 sequence resembles that of Saccharomyces cerevisiae Bfr1, which also localises to the endoplasmic reticulum and binds to ribosomal protein mRNAs. However, unlike Bfr1, ERBP1 does not bind to mRNAs encoding secreted proteins, and it is also not recruited to stress granules after starvation.

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A Molecular Titration System Coordinates Ribosomal Protein Gene Transcription with Ribosomal RNA Synthesis

Cited by 55 publications

References 38 publications

A Puzzle of Life: Crafting Ribosomal Subunits

A Puzzle of Life: Crafting Ribosomal Subunits

A ribosome assembly stress response regulates transcription to maintain proteome homeostasis

The endoplasmic reticulum-associated mRNA-binding proteins ERBP1 and ERBP2 interact in bloodstream-formTrypanosoma brucei

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