60S pre-ribosome formation viewed from assembly in the nucleolus until export to the cytoplasm

Nissan, Tracy; Baßler, Jochen; Petfalski, Elisabeth; Tollervey, David; Hurt, Ed

doi:10.1093/emboj/cdf547

Cited by 328 publications

(531 citation statements)

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“…Structural data from yeast show that Rpl10 is located at the subunit interface side of the 60S subunit in a cleft between the central protuberance and the L7/L12 stalk near the A and P sites and close to the catalytic trans-peptidyl transferase center. 14 Experimental data from yeast indicate that Rpl10 is a multifunctional component of the large subunit that is successively involved in 60S preribosome assembly in the nucleolus, 15 and in the nuclear export of the 60S subunit. The latter is functionally linked to Nmd3 via the Xpo1/exportin export receptor pathway.…”

Section: Introductionmentioning

confidence: 99%

Mutations in the ribosomal protein gene RPL10 suggest a novel modulating disease mechanism for autism

et al. 2006

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Autism has a strong genetic background with a higher frequency of affected males suggesting involvement of X-linked genes and possibly also other factors causing the unbalanced sex ratio in the etiology of the disorder. We have identified two missense mutations in the ribosomal protein gene RPL10 located in Xq28 in two independent families with autism. We have obtained evidence that the amino-acid substitutions L206M and H213Q at the C-terminal end of RPL10 confer hypomorphism with respect to the regulation of the translation process while keeping the basic translation functions intact. This suggests the contribution of a novel, possibly modulating aberrant cellular function operative in autism. Previously, we detected high expression of RPL10 by RNA in situ hybridization in mouse hippocampus, a constituent of the brain limbic system known to be afflicted in autism. Based on these findings, we present a model for autistic disorder where a change in translational function is suggested to impact on those cognitive functions that are mediated through the limbic system.

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Section: Introductionmentioning

confidence: 99%

Mutations in the ribosomal protein gene RPL10 suggest a novel modulating disease mechanism for autism

et al. 2006

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“…Following cleavage at early sites, the 90S particle gives rise to early 43S and 66S preribosomal particles, which contain 20S and 27SA pre-rRNAs, respectively. It appears that most of the factors associated with the 35S pre-rRNA, with a few exceptions, are released after the 35S pre-rRNA is split into 20S and 27SA pre-rRNAs (Grandi et al 2002;Nissan et al 2002). The early 43S preribosomal particle is rapidly exported to the cytoplasm, where the conversion of 20S pre-rRNA into mature 18S rRNA and the last assembly reactions take place (Udem and Warner 1973).…”

Section: Introductionmentioning

confidence: 99%

“…However, the study of the different purified pre-60S complexes is consistent with the presence of distinct pre-60S intermediates that move from the nucleolus to the nucleoplasm and from there to the cytoplasm. These intermediates are termed, according to their position in the pathway, early, medium, late, and cytoplasmic pre-60S r-particles Nissan et al 2002). The earliest 66S preribosomal particle is likely the result of the association of >50 nonribosomal proteins and most large r-proteins with the 27SA pre-rRNA (Nissan et al 2002).…”

Section: Introductionmentioning

confidence: 99%

“…These intermediates are termed, according to their position in the pathway, early, medium, late, and cytoplasmic pre-60S r-particles Nissan et al 2002). The earliest 66S preribosomal particle is likely the result of the association of >50 nonribosomal proteins and most large r-proteins with the 27SA pre-rRNA (Nissan et al 2002). The complexity of the pre-60S r-particles decreases during their maturation from the nucleolus to the nucleoplasm (Nissan et al 2002;Saveanu et al 2003) and the export-competent pre-60S particle has completed the pre-rRNA processing reactions (Baßler et al 2001;Nissan et al 2002).…”

Section: Introductionmentioning

confidence: 99%

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Npa1p is an essential trans-acting factor required for an early step in the assembly of 60S ribosomal subunits in Saccharomyces cerevisiae

Rosado

Cruz²

2004

RNA

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Ribosome biogenesis requires >100 nonribosomal proteins, which are associated with different preribosomal particles. The substrates, the interacting partners, and the timing of action of most of these proteins are largely unknown. To elucidate the functional environment of the putative ATP-dependent RNA helicase Dbp6p from Saccharomyces cerevisiae, which is required for 60S ribosomal subunit assembly, we have previously performed a synthetic lethal screen and thereby revealed a genetic interaction network between Dbp6p, Rpl3p, Nop8p, and the novel Rsa3p. In this report, we extended the characterization of this functional network by performing a synthetic lethal screen with the rsa3 null allele. This screen identified the so far uncharacterized Npa1p (YKL014C). Polysome profile analysis indicates that there is a deficit of 60S ribosomal subunits and an accumulation of half-mer polysomes in the slowly growing npa1-1 mutant. Northern blotting and primer extension analysis shows that the npa1-1 mutation negatively affects processing of all 27S pre-rRNAs and the normal accumulation of both mature 25S and 5.8S rRNAs. In addition, 27SA 2 pre-rRNA is prematurely cleaved at site C 2 . Moreover, GFP-tagged Npa1p localizes predominantly to the nucleolus and sediments with large complexes in sucrose gradients, which most likely correspond to pre-60S ribosomal particles. We conclude that Npa1p is required for ribosome biogenesis and operates in the same functional environment of Rsa3p and Dbp6p during early maturation of 60S ribosomal subunits.

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“…Multiple ribosomal proteins assemble with rRNA in the nucleolus and may facilitate proper processing of the pre-rRNA primary transcript (Fatica and Tollervey, 2002). Additionally, a significant number of nonribosomal proteins bind to these formative ribosomes in the nucleolus and also in the nucleoplasm after the nascent ribosomal subunits leave the nucleolus Kuersten et al, 2001;Nissan et al, 2002). The binding of particular proteins in a prescribed order is probably necessary for nucleocytoplasmic transport of the processed ribosomal subunits (e.g., Milkereit et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Diffusion-based Transport of Nascent Ribosomes in the Nucleus

Politz

Tuft

Pederson

2003

MBoC

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Although the complex process of ribosome assembly in the nucleolus is beginning to be understood, little is known about how the ribosomal subunits move from the nucleolus to the nuclear membrane for transport to the cytoplasm. We show here that large ribosomal subunits move out from the nucleolus and into the nucleoplasm in all directions, with no evidence of concentrated movement along directed paths. Mobility was slowed compared with that expected in aqueous solution in a manner consistent with anomalous diffusion. Once nucleoplasmic, the subunits moved in the same random manner and also sometimes visited another nucleolus before leaving the nucleus. INTRODUCTIONIn eukaryotes, rRNA transcription and ribosome assembly take place in the nucleolus. Nascent ribosomes then exit the nucleolus and move into the cytoplasm. Multiple ribosomal proteins assemble with rRNA in the nucleolus and may facilitate proper processing of the pre-rRNA primary transcript (Fatica and Tollervey, 2002). Additionally, a significant number of nonribosomal proteins bind to these formative ribosomes in the nucleolus and also in the nucleoplasm after the nascent ribosomal subunits leave the nucleolus Kuersten et al., 2001;Nissan et al., 2002). The binding of particular proteins in a prescribed order is probably necessary for nucleocytoplasmic transport of the processed ribosomal subunits (e.g., Milkereit et al., 2001). The nuclear export of both the large and small ribosomal subunits has been shown to be dependent, at least indirectly, on the Ran-GTPase cycle and the exportin CRM1, and it is likely that CRM1-mediated export of 60S subunits requires the adaptor protein NMD3 (Moy and Silver, 1999;Ho et al., 2000;Gadal et al., 2001;Thomas and Kutay, 2003;Trotta et al., 2003). In situ hybridization experiments in fission yeast have indicated that rRNA may accumulate along short tracks when near the nuclear pores but nonetheless appears to exit from all the pores, not just those near the nucleolus (Léger-Silvestre et al., 1999). In situ hybridization studies in mammalian cells have primarily addressed the distribution of rRNA within the nucleolus (Huang, 2002) rather than the routes of extranucleolar rRNA traffic, because although high signal representing rRNA is routinely detected in both the nucleolus and the cytoplasm, nucleoplasmic signal which might represent ribosomes moving to the nuclear periphery is not easily detectable by in situ hybridization (PuvionDutilleul et al., 1991;Lazdins et al., 1997; J.C.R. Politz, unpublished observations). Therefore, very little is known about the spatial pattern or mechanism of rRNA movement from the nucleolus into the nucleoplasm and then to the nuclear pores for export (Cullen, 2000;Kuersten et al., 2001;Lei and Silver, 2002), although all three classes of eukaryotic RNAs, rRNA, mRNA, and pol III transcripts have been shown to exit from all the nuclear pores (Dworetzky and Feldherr, 1988;Pante et al., 1997;Mattaj and Englmeier, 1998).In previous studies in live cells (Politz et al., 1998, we investigat...

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60S pre-ribosome formation viewed from assembly in the nucleolus until export to the cytoplasm

Cited by 328 publications

References 45 publications

Mutations in the ribosomal protein gene RPL10 suggest a novel modulating disease mechanism for autism

Mutations in the ribosomal protein gene RPL10 suggest a novel modulating disease mechanism for autism

Npa1p is an essential trans-acting factor required for an early step in the assembly of 60S ribosomal subunits in Saccharomyces cerevisiae

Diffusion-based Transport of Nascent Ribosomes in the Nucleus

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