Nop53p is a novel nucleolar 60S ribosomal subunit biogenesis protein

Sydorskyy, Yaroslav; Dilworth, David; Halloran, Brendan P.; Yi, Eugene C.; Makhnevych, Taras; Wozniak, Richard W.; Aitchison, John D.

doi:10.1042/bj20041297

Cited by 35 publications

(38 citation statements)

References 50 publications

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“…A similar phenomena is frequently observed in yeast when the processing of the 60 S subunit is altered (18,73,74). The mechanisms by which this occurs is not yet elucidated, but altogether these observations strongly support the notion that in mammals, like in yeast, there is some form of negative feedback on the processing machinery when the ribosome biogenesis is altered (75).…”

Section: Isg20l2 Interacts With Ribosomal Proteins and Proteins Involsupporting

confidence: 67%

ISG20L2, a Novel Vertebrate Nucleolar Exoribonuclease Involved in Ribosome Biogenesis

Couté

Kindbeiter²,

Belin

et al. 2008

Molecular & Cellular Proteomics

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Proteomics analyses of human nucleoli provided molecular bases for an understanding of the multiple functions fulfilled by these nuclear domains. However, the biological roles of about 100 of the identified proteins are unpredictable. The present study describes the functional characterization of one of these proteins, ISG20L2. We demonstrate that ISG20L2 is a 3 to 5 exoribonuclease involved in ribosome biogenesis at the level of 5.8 S rRNA maturation, more specifically in the processing of the 12 S precursor rRNA. The use of truncated forms of ISG20L2 demonstrated that its N-terminal half promotes the nucleolar localization and suggested that its C-terminal half bears the exoribonuclease activity. Nuclei of eukaryotic cells are highly organized organelles in which more than 30 different kinds of transient structures, called nuclear domains or nuclear bodies, support the nuclear functions (1). Since the 1960s, it has been known that nucleoli, the most prominent of the nuclear domains, are the sites of ribosome biogenesis. This function gives rise to their characteristic ultrastructural organization in three main compartments, the fibrillar center and the dense fibrillar and granular components (2).Ribosome biogenesis is a very complex process that involves the synthesis of ribosomal RNAs (rRNAs) 1 coupled with their extensive processing, the assembly of these rRNAs with ribosomal proteins, and the export of the resulting preribosomal subunits from nuclei to cytoplasm where the final maturation occurs (3). rRNA processing mainly consists of base modifications and cleavages (4). Precursor rRNAs (pre-rRNAs) contain external and internal sequences that are not present within mature rRNAs. Removal of these sequences is achieved through sequential endonucleolytic and exonucleolytic cleavages, producing mature 18 S, 5.8 S, and 28 S rRNAs. Studies in yeast have identified several factors responsible for such cleavages: the ribonucleoprotein complex RNase MRP and Ngl2p catalyzing endoribonucleolytic processing, Xrn1p and Rat1p that are 5Ј to 3Ј exonucleases, Rex1p and Rex2p that are 3Ј to 5Ј exonucleases, and a protein complex named exosome composed of 3Ј to 5Ј exoribonucleases and putative RNA-binding proteins (5-9). However, the list of the catalytic factors required for the complete processing of pre-rRNAs into mature species is still incomplete.Correct rRNA maturation that provides finely folded and packaged mature rRNAs is crucial because it is highly probable that eukaryotic ribosomes are, as it has clearly been demonstrated for prokaryote ribosomes, ribozymes (10, 11). In yeast, incorrectly maturated rRNAs lead to translational infidelity of ribosomes (12). In mammals, defects in pre-rRNA processing are therefore likely to entail the development of severe pathologies. Indeed results on DKC1, the gene altered in dyskeratosis congenita, indicated that altered rRNA processing plays a direct role in tumorigenesis (13). Recently Gleizes and co-workers (14) showed that ribosome biogenesis and notably pre-rRNA processing...

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Section: Isg20l2 Interacts With Ribosomal Proteins and Proteins Involsupporting

confidence: 67%

ISG20L2, a Novel Vertebrate Nucleolar Exoribonuclease Involved in Ribosome Biogenesis

Couté

Kindbeiter²,

Belin

et al. 2008

Molecular & Cellular Proteomics

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“…1A to D). This is in stark contrast to the results of other studies, where the knockdown of ribosome biogenesis proteins resulted in a concomitant reduction in cytosolic 80S ribosome levels (23,24). Our decreased ratio of polysomes/monoribosomes suggests a significant flaw in translation initiation following DHX33 knockdown (25,26).…”

Section: Dhx33contrasting

confidence: 57%

The DHX33 RNA Helicase Promotes mRNA Translation Initiation

Zhang

You

Wang

et al. 2015

Molecular and Cellular Biology

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b DEAD/DEAH box RNA helicases play essential roles in numerous RNA metabolic processes, such as mRNA translation, premRNA splicing, ribosome biogenesis, and double-stranded RNA sensing. Herein we show that a recently characterized DEAD/ DEAH box RNA helicase, DHX33, promotes mRNA translation initiation. We isolated intact DHX33 protein/RNA complexes in cells and identified several ribosomal proteins, translation factors, and mRNAs. Reduction of DHX33 protein levels markedly reduced polyribosome formation and caused the global inhibition of mRNA translation that was rescued with wild-type DHX33 but not helicase-defective DHX33. Moreover, we observed an accumulation of mRNA complexes with the 80S ribosome in the absence of functional DHX33, consistent with a stalling in initiation, and DHX33 more preferentially promoted structured mRNA translation. We conclude that DHX33 functions to promote elongation-competent 80S ribosome assembly at the late stage of mRNA translation initiation. Our results reveal a newly recognized function of DHX33 in mRNA translation initiation, further solidifying its central role in promoting cell growth and proliferation. Mammalian cells maintain tight control of global mRNA translation through the production of ribosomes (1, 2); deregulation in mRNA translation is frequently found in human diseases (3-6) and is regarded as one of the many factors contributing to cancer development (7-9).Most eukaryotic protein translation initiation occurs by an ordered assembly of a preinitiation complex on the 5= cap of mRNA (10). After mature mRNA is transported into the cytosol, the distinct 5= cap of mRNA is recognized and bound by a large protein complex comprising eukaryotic initiation factor 4E (eIF4E), eIF4A, and eIF4G as well as poly(A)-binding protein (PABP) (1,11,12). These factors coordinately prevent mRNA degradation while priming mRNAs for translation initiation.The initial step in mRNA translation involves formation of a ternary complex between eIF2-GTP, Met-tRNA interference, and small 40S ribosomal subunits. This process is stimulated by the translation initiation factors eIF1, eIF3, eIF4F, and eIF5 (13). This large complex, termed the 43S preinitiation complex, attaches to the activated 5= cap of mRNA. Bound RNA helicases are responsible for unwinding various secondary structures in mRNA as the complex scans along the mRNA from the 5= end to the 3= end until it finds the initiation codon. The 60S large ribosome subunit then joins with the 40S subunit to form an 80S ribosome under guidance from eIF5B-GTP (2, 13). eIF2-GTP and eIF5B-GTP are then hydrolyzed into their GDP forms to promote the assembly of the functional initiation complex (14). The detailed mechanism of how elongation-competent 80S ribosomes are assembled prior to initiation or what triggers initiation is not well understood.Mammalian mRNAs often contain highly structured untranslated regions (UTRs) at the 5= ends of their open reading frame sequences that must be unwound to allow ribosome recruitment and scanning. Not su...

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“…Each of these proteins was specifically depleted of early and intermediate pre-LSU populations purified by Noc2-TAP indicating that these proteins mark pre-LSU populations from which Noc2 had already dissociated (Figure 3B, lanes 1-10). Depletion of each of the three proteins was previously shown to result in delay in nuclear processing of 27SB and 7S pre-rRNAs, which are major rRNA precursor components of the pre-ribosomal populations they are associated with ( [53,75,81–83], see also Figure 2 lanes 7-9). A direct comparison of pre-ribosomes purified by Nog2-TAP, Rsa4-TAP or Nop53-TAP indicated that their respective protein (Figure 3B, lanes 11-13) and pre-rRNA (Figure 2, lanes 7-9) composition was highly similar, and largely differed from the one of Noc2-TAP associated pre-ribosomes.…”

Section: Resultsmentioning

confidence: 95%

Studies on the Assembly Characteristics of Large Subunit Ribosomal Proteins in S. cerevisae

et al. 2013

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During the assembly process of ribosomal subunits, their structural components, the ribosomal RNAs (rRNAs) and the ribosomal proteins (r-proteins) have to join together in a highly dynamic and defined manner to enable the efficient formation of functional ribosomes. In this work, the assembly of large ribosomal subunit (LSU) r-proteins from the eukaryote S. cerevisiae was systematically investigated. Groups of LSU r-proteins with specific assembly characteristics were detected by comparing the protein composition of affinity purified early, middle, late or mature LSU (precursor) particles by semi-quantitative mass spectrometry. The impact of yeast LSU r-proteins rpL25, rpL2, rpL43, and rpL21 on the composition of intermediate to late nuclear LSU precursors was analyzed in more detail. Effects of these proteins on the assembly states of other r-proteins and on the transient LSU precursor association of several ribosome biogenesis factors, including Nog2, Rsa4 and Nop53, are discussed.

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Nop53p is a novel nucleolar 60S ribosomal subunit biogenesis protein

Cited by 35 publications

References 50 publications

ISG20L2, a Novel Vertebrate Nucleolar Exoribonuclease Involved in Ribosome Biogenesis

ISG20L2, a Novel Vertebrate Nucleolar Exoribonuclease Involved in Ribosome Biogenesis

The DHX33 RNA Helicase Promotes mRNA Translation Initiation

Studies on the Assembly Characteristics of Large Subunit Ribosomal Proteins in S. cerevisae

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