The p20 and Ded1 proteins have antagonistic roles in eIF4E-dependent translation in
            <i>Saccharomyces cerevisiae</i>

Cruz, Jesús de la; Iost, Isabelle; Kressler, Dieter; Linder, Patrick

doi:10.1073/pnas.94.10.5201

Cited by 198 publications

(90 citation statements)

References 49 publications

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“…Unexpectedly, we observed the appearance of a huge 80S peak in the dominant mutant and reduced polysomes (Figure 4e). Such a ribosomal profile on sucrose gradients is reminiscent of mutants with defects in translation initiation (32–35). However, when the intragenic rio1 D244A + CΔ46 suppressor allele was analyzed in a similar way, 20S>18S rRNA processing and a normal polysome profile were restored (Figure 4e and data not shown).…”

Section: Resultsmentioning

confidence: 99%

Dominant Rio1 kinase/ATPase catalytic mutant induces trapping of late pre-40S biogenesis factors in 80S-like ribosomes

et al. 2014

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During eukaryotic ribosome biogenesis, members of the conserved atypical serine/threonine protein kinase family, the RIO kinases (Rio1, Rio2 and Rio3) function in small ribosomal subunit biogenesis. Structural analysis of Rio2 indicated a role as a conformation-sensing ATPase rather than a kinase to regulate its dynamic association with the pre-40S subunit. However, it remained elusive at which step and by which mechanism the other RIO kinase members act. Here, we have determined the crystal structure of the human Rio1–ATP–Mg2+ complex carrying a phosphoaspartate in the active site indicative of ATPase activity. Structure-based mutations in yeast showed that Rio1's catalytic activity regulates its pre-40S association. Furthermore, we provide evidence that Rio1 associates with a very late pre-40S via its conserved C-terminal domain. Moreover, a rio1 dominant-negative mutant defective in ATP hydrolysis induced trapping of late biogenesis factors in pre-ribosomal particles, which turned out not to be pre-40S but 80S-like ribosomes. Thus, the RIO kinase fold generates a versatile ATPase enzyme, which in the case of Rio1 is activated following the Rio2 step to regulate one of the final 40S maturation events, at which time the 60S subunit is recruited for final quality control check.

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Section: Resultsmentioning

confidence: 99%

Dominant Rio1 kinase/ATPase catalytic mutant induces trapping of late pre-40S biogenesis factors in 80S-like ribosomes

et al. 2014

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“…However, in contrast to dbp1, ded1 mutation is lethal. Despite this, it is believed that Ded1p and Dbp1p have related functions since over-expression of Dbp1p can suppress ded1 mutation [68] and both proteins function in translation initiation [74][75][76]. Ded1p functions in cooperation with another DEAD box protein eIF4A (Tif2p), one of the components of the initiation factor eIF4E complex [77], to stabilize 40S ribosomal subunit scanning of the 5'UTR until it reaches the first AUG codon.…”

Section: Ddx3 Functions In Protein Synthesismentioning

confidence: 98%

“…DDX3 homologues were studied in two yeast models: Saccharomyces cerevisiae and Schizosaccharomyces pombe [74][75][76]. In S. cerevisiae, the paralogous proteins Ded1p and Dbp1p have 71% identity.…”

Section: Ddx3 Functions In Protein Synthesismentioning

confidence: 99%

The DDX3 Subfamily of the DEAD Box Helicases: Divergent Roles as Unveiled by Studying Different Organisms and In Vitro Assays

Rosner

Rinkevich

2007

CMC

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DDX3 (or Ded1p), the highly conserved subfamily of the DEAD-box RNA helicase family (40 members in humans), plays important roles in RNA metabolism. DDX3X and DDX3Y, the two human paralogous genes of this subfamily of proteins, have orthologous candidates in a diverse range of eukaryotes, from yeast and plants to animals. While DDX3Y, which is essential for normal spermatogenesis, is translated only in the testes, DDX3X protein is ubiquitously expressed, involved in RNA transcription, RNA splicing, mRNA transport, translation initiation and cell cycle regulation. Studies of recent years have revealed that DDX3X participates in HIV and hepatitis C viral infections, and in hepatocellular carcinoma, a complication of hepatitis B and hepatitis C infections. In the urochordates (i.e., Botryllus schlosseri) and in diverse invertebrate phyla (represented by model organisms such as: Drosophila, Hydra, Planaria), DDX3 proteins (termed also PL10) are involved in developmental pathways, highly expressed in adult undifferentiated soma and germ cells and in some adult and embryo's differentiating tissues. As the mechanistic and functional knowledge of DDX3 proteins is limited, we suggest assembling the available data on DDX3 proteins, from all studied organisms and in vitro assays, depicting a unified mechanistic scheme for DDX3 proteins' functions. Understanding the diverse functions of DDX3 in multicellular organisms may be particularly important for effective strategies of drug design.

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“…These proteins function in the TOR kinase signaling pathway that controls the rate of translation initiation during the cell cycle (10). TOR signaling is sensitive to rapamycin, and mutations that impair the function of some proteins that function in the TOR pathway, such as Eap1p, confer resistance to rapamycin (5).…”

Section: Discussionmentioning

confidence: 99%

Ebs1p, a Negative Regulator of Gene Expression Controlled by the Upf Proteins in the Yeast Saccharomyces cerevisiae

et al. 2006

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Mutations in EBS1 were identified in Saccharomyces cerevisiae that cosuppress missense, frameshift, and nonsense mutations. Evidence from studies of loss of function and overexpression of EBS1 suggests that Ebs1p affects gene expression by inhibiting translation and that a loss of EBS1 function causes suppression by increasing the rate of translation. Changes in EBS1 expression levels alter the expression of wild-type genes, but, in general, no changes in mRNA abundance were associated with a loss of function or overexpression of EBS1. Translation of a lacZ reporter was increased in strains carrying an ebs1-⌬ mutant gene, whereas translation was decreased when EBS1 was overexpressed. The cap binding protein eIF-4E copurifies with Ebs1p in the absence of RNA, suggesting that the two proteins interact in vivo. Although physical and genetic interactions were detected between Ebs1p and Dcp1p, copurification was RNase sensitive, and changes in the expression of Ebs1p had little to no effect on decapping of the MFA2 transcript. The combined results suggest that Ebs1p inhibits translation, most likely through effects on eIF-4E rather than on decapping. Finally, EBS1 transcript levels are under the control of nonsense-mediated mRNA decay (NMD), providing the first example of an NMD-sensitive transcript whose protein product influences a step in gene expression required for NMD.All eukaryotes have a nonsense-mediated mRNA decay (NMD) pathway that monitors the fidelity of gene expression at the level of RNA surveillance (6). One purpose served by NMD is to identify and degrade transcripts containing errors that cause premature termination of translation, which limits the accumulation of potentially deleterious truncated proteins (40). The UPF genes, which were first identified in Saccharomyces cerevisiae (8,26,27), are represented by orthologs in widely divergent evolutionary branches of the eukaryotes (6) but are absent in prokaryotes and archaea. In addition to RNA surveillance, the Upf proteins control the abundance of hundreds of transcripts in S. cerevisiae (18,28).The mechanism of nonsense transcript decay is intimately related to translation and decapping (31, 49). The Upf proteins and the translation termination factors eRF1 and eRF3 are assembled in a surveillance complex that is recruited to nonsense transcripts to catalyze termination at a premature stop codon, followed by decapping and decay (for a recent summary, see reference 7). Upf1p interacts with the decapping enzyme Dcp2p to promote Xrn1p-mediated decay from the 5Ј end (17, 36) and with Ski7p to promote exosome-mediated decay from the 3Ј end (32, 45). Although the broad outlines of the circuitry leading to NMD are known, the manner in which the surveillance complex affects the interplay between mRNA decay and translation is still unclear.To better understand the relationship between NMD and translation, we devised a selection method to uncover rare hypomorphic mutations in genes coding for either translation factors or additional Upf proteins. The possi...

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The p20 and Ded1 proteins have antagonistic roles in eIF4E-dependent translation in Saccharomyces cerevisiae

Cited by 198 publications

References 49 publications

Dominant Rio1 kinase/ATPase catalytic mutant induces trapping of late pre-40S biogenesis factors in 80S-like ribosomes

Dominant Rio1 kinase/ATPase catalytic mutant induces trapping of late pre-40S biogenesis factors in 80S-like ribosomes

The DDX3 Subfamily of the DEAD Box Helicases: Divergent Roles as Unveiled by Studying Different Organisms and In Vitro Assays

Ebs1p, a Negative Regulator of Gene Expression Controlled by the Upf Proteins in the Yeast Saccharomyces cerevisiae

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