Mapping the Functional Domains of Yeast NMD3, the Nuclear Export Adapter for the 60 S Ribosomal Subunit

Hedges, John; Chen, Yen-I; West, Matthew; Bussiere, Cyril; Johnson, Arlen

doi:10.1074/jbc.m606798200

Cited by 24 publications

(30 citation statements)

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“…T25G3.3 encodes the C. elegans homolog of NMD3, which has been shown to function in NMD by interacting with UPF1 (He and Jacobson, 1995). NMD3 is also essential for nuclear export of the 60S ribosomal subunit (Hedges et al, 2006). As expected, T25G3.3 interacts with ribosomal subunits (e.g.…”

Section: © Higher Education Press and Springer-verlag Berlin Heidelbesupporting

confidence: 59%

“…Mutant alleles of NMD3 also show altered rRNA stability. NMD3 colocalizes with the 60S ribosome subunit and is required for its nuclear export (Hedges et al, 2006). Our results showed that NMD is regulated by vesicle-mediated trafficking, cytoskeleton proteins, extracellular matrix components and ubiquitin-mediated protein degradation, although the underlying mechanism for their role in NMD has yet to be elucidated.…”

Section: Regulation Of Nmd By Various Biological Processesmentioning

confidence: 73%

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A genome-wide RNAi screen identifies genes regulating the formation of P bodies in C. elegans and their functions in NMD and RNAi

et al. 2011

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Cytoplasmic processing bodies, termed P bodies, are involved in diverse post-transcriptional processes including mRNA decay, nonsense-mediated RNA decay (NMD), RNAi, miRNA-mediated translational repression and storage of translationally silenced mRNAs. Regulation of the formation of P bodies in the context of multicellular organisms is poorly understood. Here we describe a systematic RNAi screen in C. elegans that identified 224 genes with diverse cellular functions whose inactivations result in a dramatic increase in the number of P bodies. 83 of these genes form a complex functional interaction network regulating NMD. We demonstrate that NMD interfaces with many cellular processes including translation, ubiquitin-mediated protein degradation, intracellular trafficking and cytoskeleton structure. We also uncover an extensive link between translation and RNAi, with different steps in protein synthesis appearing to have distinct effects on RNAi efficiency. Moreover, the intracellular vesicular trafficking network plays an important role in the regulation of RNAi. A subset of genes enhancing P body formation also regulate the formation of stress granules in C. elegans. Our study offers insights into the cellular mechanisms that regulate the formation of P bodies and also provides a framework for system-level understanding of NMD and RNAi in the context of the development of multicellular organisms.

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Section: © Higher Education Press and Springer-verlag Berlin Heidelbesupporting

confidence: 59%

Section: Regulation Of Nmd By Various Biological Processesmentioning

confidence: 73%

A genome-wide RNAi screen identifies genes regulating the formation of P bodies in C. elegans and their functions in NMD and RNAi

et al. 2011

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“…This alignment gives a consensus leucine-rich NES and suggests that although the NES is highly conserved throughout eukaryotes, it has shifted slightly in position during evolution. Changing leucine 505 to alanine (nmd3L505A) had a strong effect on the localization of Nmd3 and cell growth (Hedges et al, 2006) and was synthetic lethal with arx1⌬ (data not shown). Thus, deletion of ARX1 is synthetic lethal with a defect in Nmd3 export function.…”

Section: Genetic Interactions Of Arx1mentioning

confidence: 99%

Arx1 Is a Nuclear Export Receptor for the 60S Ribosomal Subunit in Yeast

Hung

Patel

et al. 2008

MBoC

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We previously showed that nuclear export of the large (60S) ribosomal subunit relies on Nmd3 in a Crm1-dependent manner. Recently the general mRNA export factor, the Mtr2/Mex67 heterodimer, was shown to act as an export receptor in parallel with Crm1. These observations raise the possibility that nuclear export of the 60S subunit in Saccharomyces cerevisiae requires multiple export receptors. Here, we show that the previously characterized 60S subunit biogenesis factor, Arx1, also acts as an export receptor for the 60S subunit. We found that deletion of ARX1 was synthetic lethal with nmd3 and mtr2 mutants and was synthetic sick with several nucleoporin mutants. Deletion of ARX1 led to accumulation of pre-60S particles in the nucleus that were enriched for Nmd3, Crm1, Mex67, and Mtr2, suggesting that in the absence of Arx1, 60S export is impaired even though the subunit is loaded with export receptors. Finally, Arx1 interacted with several nucleoporins in yeast two-hybrid as well as in vitro assays. These results show that Arx1 can directly bridge the interaction between the pre-60S particle and the NPC and thus is a third export receptor for the 60S subunit in yeast.

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“…pAJ693 was constructed by moving the deletion from pAJ516 to pAJ690. pAJ1298, pAJ1403 and pAJ1404 were isolated as described (25). To create plasmids pAJ1406, pAJ1407, and pAJ1408, pAJ1298, pAJ1403, and pAJ1404, respectively, were cut with PacI and SpeI and co-transformed into wild-type strain W303 with BsgIBspHI-digested pAJ582.…”

Section: Methodsmentioning

confidence: 99%

“…11 and 24). Deletion or mutation of this NES results in the nuclear accumulation of both Nmd3 and nascent 60S ribosomal subunits (20,21,25).…”

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confidence: 99%

Novel Interaction of the 60S Ribosomal Subunit Export Adapter Nmd3 at the Nuclear Pore Complex

West¹,

Hedges²,

et al. 2007

Journal of Biological Chemistry

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Nuclear export of the large (60S) ribosomal subunit depends on the adapter protein Nmd3 to provide a nuclear export signal (NES). The leucine-rich NES is recognized by the export receptor Crm1 to mediate export via interaction with the nuclear pore complex (NPC). Here, we show that certain mutant Nmd3 proteins that are impaired for binding to the 60S subunit accumulate at the nuclear envelope. These mutant proteins also show enhanced binding to Crm1, both in vivo and in vitro. Although their interaction with the NPC is dependent on recognition of the NES by Crm1, their interaction with Crm1 is not strictly dependent on RanGTP. Using a collection of GFP-tagged nucleoporin mutants, we identified several nucleoporins, including components of the Nup82 complex that copurified with the mutant Nmd3. The Nup82 complex is on the cytoplasmic face of the NPC and has previously been shown to be important as a terminal binding site for Crm1-mediated export. Mutations in the Nup82 complex led to accumulation of wild-type Nmd3 in the nucleoplasm, suggesting that the interaction of mutant Nmd3 with the Nup82 complex reflects a defect in the bona fide export pathway for the 60S subunit. These results suggest that in the absence of the ribosome, Nmd3 is not efficiently released from Crm1 at the NPC.

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Mapping the Functional Domains of Yeast NMD3, the Nuclear Export Adapter for the 60 S Ribosomal Subunit

Cited by 24 publications

References 24 publications

A genome-wide RNAi screen identifies genes regulating the formation of P bodies in C. elegans and their functions in NMD and RNAi

A genome-wide RNAi screen identifies genes regulating the formation of P bodies in C. elegans and their functions in NMD and RNAi

Arx1 Is a Nuclear Export Receptor for the 60S Ribosomal Subunit in Yeast

Novel Interaction of the 60S Ribosomal Subunit Export Adapter Nmd3 at the Nuclear Pore Complex

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