Eukaryotic Ribosome Assembly and Nuclear Export

Nerurkar, Purnima; Altvater, Martin; Gerhardy, Stefan; Schütz, Sabina; Fischer, Ute; Weirich, Christine S.; Panse, Vikram Govind

doi:10.1016/bs.ircmb.2015.07.002

Cited by 98 publications

(87 citation statements)

References 153 publications

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“…Due to the large size of the pre-40S ribosome, it is predicted that multiple export factors are required to facilitate its rapid translocation [70]. Pre-40S export depends on the GTPase Gsp1/Ran and Crm1/Xpo1, the general exportin for substrates harboring nuclear export signal (NES) sequences [5,10,71,72]. At least three biogenesis factors (Dim2, Ltv1, and Rio2) contain predicted or functional NESs that are, possibly due to their redundancy, individually not required for pre-40S export [5,10].…”

Section: Final Maturation Of Pre-40s Particlesmentioning

confidence: 99%

“…Pre-40S export depends on the GTPase Gsp1/Ran and Crm1/Xpo1, the general exportin for substrates harboring nuclear export signal (NES) sequences [5,10,71,72]. At least three biogenesis factors (Dim2, Ltv1, and Rio2) contain predicted or functional NESs that are, possibly due to their redundancy, individually not required for pre-40S export [5,10]. Additionally, several other factors have been implicated in the export of pre-40S subunits [10], but their direct role in this process remains vague.…”

Section: Final Maturation Of Pre-40s Particlesmentioning

confidence: 99%

“…Nuclear Export and Cytoplasmic Maturation of Pre-60S Ribosomes Several export-mediating factors interact with different surfaces of pre-60S ribosomes to mediate their efficient translocation across the NPC [5,10,14,103] (Figures 2O and 5). Following the release of Nog2, the export adaptor Nmd3 binds in the A-, P-, and E-tRNA-binding sites of the LSU and recruits the exportin Crm1/Xpo1 via its essential NES sequences [10,14,30,32,101].…”

Section: Assembly Of the Lsumentioning

confidence: 99%

“…Following the release of Nog2, the export adaptor Nmd3 binds in the A-, P-, and E-tRNA-binding sites of the LSU and recruits the exportin Crm1/Xpo1 via its essential NES sequences [10,14,30,32,101]. Thus, Nmd3 appears to sense the correct conformation around the PTC and prevents premature tRNA binding [30,32].…”

Section: Assembly Of the Lsumentioning

confidence: 99%

“…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].…”

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confidence: 99%

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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: Final Maturation Of Pre-40s Particlesmentioning

confidence: 99%

Section: Final Maturation Of Pre-40s Particlesmentioning

confidence: 99%

Section: Assembly Of the Lsumentioning

confidence: 99%

Section: Assembly Of the Lsumentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

A Puzzle of Life: Crafting Ribosomal Subunits

Kressler

Hurt

Baßler

2017

Trends in Biochemical Sciences

164

127

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KMT2D Deficiency Promotes Myeloid Leukemias which Is Vulnerable to Ribosome Biogenesis Inhibition

Zhong

Zhang

et al. 2023

Advanced Science

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KMT2C and KMT2D are the most frequently mutated epigenetic genes in human cancers. While KMT2C is identified as a tumor suppressor in acute myeloid leukemia (AML), the role of KMT2D remains unclear in this disease, though its loss promotes B cell lymphoma and various solid cancers. Here, it is reported that KMT2D is downregulated or mutated in AML and its deficiency, through shRNA knockdown or CRISPR/Cas9 editing, accelerates leukemogenesis in mice. Hematopoietic stem and progenitor cells and AML cells with Kmt2d loss have significantly enhanced ribosome biogenesis and consistently, enlarged nucleolus, increased rRNA and protein synthesis rates. Mechanistically, it is found that KMT2D deficiency leads to the activation of the mTOR pathway in both mouse and human AML cells. Kmt2d directly regulates the expression of Ddit4, a negative regulator of the mTOR pathway. Consistent with the abnormal ribosome biogenesis, it is shown that CX‐5461, an inhibitor of RNA polymerase I, significantly restrains the growth of AML with Kmt2d loss in vivo and extends the survival of leukemic mice. These studies validate KMT2D as a de facto tumor suppressor in AML and reveal an unprecedented vulnerability to ribosome biogenesis inhibition.

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Construction of A High‐Flux Protein Transport Channel Inspired by the Nuclear Pore Complex

et al. 2021

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Inspired by the nuclear pore complex (NPC), herein we have established a biomimetic high-flux protein delivery system via the ingenious introduction of pillar [5]arene-based host-guest system into one side of artificial hour-glass shaped nanochannel. With a transport flux of 660 lysozymes per minute, the system provides efficient high-flux protein transport at a rate which is significantly higher than that of an unmodified nanochannel and conventional bilateral symmetrical modified nanochannels. In view of these promising results, the use of artificial nanochannel to improve protein transport not only presents a new potential chemical model for biological research and better understanding of protein transport behavior in the living systems, but also provides a highflux protein transporter device, which may have applications in the design of protein drug release systems, protein separation systems and microfluidics in the near future.

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Eukaryotic Ribosome Assembly and Nuclear Export

Cited by 98 publications

References 153 publications

A Puzzle of Life: Crafting Ribosomal Subunits

A Puzzle of Life: Crafting Ribosomal Subunits

KMT2D Deficiency Promotes Myeloid Leukemias which Is Vulnerable to Ribosome Biogenesis Inhibition

Construction of A High‐Flux Protein Transport Channel Inspired by the Nuclear Pore Complex

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