Distinct Functional Domains within Nucleoporins Nup153 and Nup98 Mediate Transcription-dependent Mobility

Griffis, Eric R.; Craige, Branch; Dimaano, Christian; Ullman, Katharine S.; Powers, Maureen A.

doi:10.1091/mbc.e03-10-0743

Cited by 111 publications

(118 citation statements)

References 43 publications

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“…Initially, a subset of Nups was found to be mobile, able to move off and on the pore (16). The intranuclear accumulation of one such Nup, Nup98, is linked to ongoing nuclear transcription and chemical inhibition of RNA polymerase II was shown to abrogate its intranuclear mobility (17,18). Moreover, Nup98 was subsequently found to directly control gene expression of a subset of developmentally regulated genes (19)(20)(21).…”

mentioning

confidence: 99%

Nup98 promotes antiviral gene expression to restrict RNA viral infection in Drosophila

Panda

Pascual-Garcia²,

Dunagin

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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In response to infection, the innate immune system rapidly activates an elaborate and tightly orchestrated gene expression program to induce critical antimicrobial genes. While many key players in this program have been identified in disparate biological systems, it is clear that there are additional uncharacterized mechanisms at play. Our previous studies revealed that a rapidly-induced antiviral gene expression program is active against disparate human arthropod-borne viruses in Drosophila. Moreover, one-half of this program is regulated at the level of transcriptional pausing. Here we found that Nup98, a virus-induced gene, was antiviral against a panel of viruses both in cells and adult flies since its depletion significantly enhanced viral infection. Mechanistically, we found that Nup98 promotes antiviral gene expression in Drosophila at the level of transcription. Expression profiling revealed that the virus-induced activation of 36 genes was abrogated upon loss of Nup98; and we found that a subset of these Nup98-dependent genes were antiviral. These Nup98-dependent virus-induced genes are Cdk9-dependent and translation-independent suggesting that these are rapidly induced primary response genes. Biochemically, we demonstrate that Nup98 is directly bound to the promoters of virus-induced genes, and that it promotes occupancy of the initiating form of RNA polymerase II at these promoters, which are rapidly induced on viral infection to restrict human arboviruses in insects.innate immunity | nuclear pore | nucleoporin | pol II regulation | P-TEFb

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mentioning

confidence: 99%

Nup98 promotes antiviral gene expression to restrict RNA viral infection in Drosophila

Panda

Pascual-Garcia²,

Dunagin

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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“…A cell needs to accurately segregate not only the genetic material and all the organelles but also the NE membranes with its specific protein components. According to the ERretention model (Collas and Courvalin, 2000), some NE components are retained in the mitotic ER network during cell division, but numerous other ones localize to diverse mitotic structures and play crucial roles in consecutive stages of the division process (Rabut and Ellenberg, 2001;Griffis et al, 2004;Xu et al, 2008;Lee et al, 2009). Both the localization patterns and a variety of developmental phenotypes point to these functions.…”

Section: Dual Roles Of Ne Components During Mitosismentioning

confidence: 99%

“…Tobacco NbRae1, a homolog of Rae1/mrnp41 in metazoans, Gle2p (for GLFG lethal 2p) in Saccharomyces cerevisiae, and Rae1 in Schizosaccharomyces pombe, exhibits a mitotic function besides its role as an mRNA export factor associated with the NPC (Whalen et al, 1997;Pritchard et al, 1999;Griffis et al, 2004;Lee et al, 2009). Mammalian Rae1 is a mitotic spindle checkpoint component in conjunction with Bub3 and forms a complex with Nup98 and the Cdh1-activated anaphasepromoting complex, preventing the degradation of Securin before anaphase (Whalen et al, 1997;Babu et al, 2003;Jeganathan et al, 2005).…”

Section: Metaphasementioning

confidence: 99%

Dynamics of the Plant Nuclear Envelope and Nuclear Pore

2011

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“…Nup153 has also been found to be essential for the localization of other pore components (19) and is specifically thought to anchor the basket constituent TPR (20). Somewhat paradoxically, Nup153 has been shown to be dynamically localized to the nuclear pore (21,22). This apparent contradiction, as well as the multiple roles implicated for Nup153, may be reconciled by the presence of distinct populations of this pore protein.…”

mentioning

confidence: 99%

“…Indeed, an analysis of Nup153 mobility indicated that a fraction of Nup153 is stably associated with the pore (Ref. 22, see also Ref. 21).…”

mentioning

confidence: 99%

Sequence Preference in RNA Recognition by the Nucleoporin Nup153

Ball¹,

Dimaano²,

Bilak

et al. 2007

Journal of Biological Chemistry

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The vertebrate nuclear pore protein Nup153 contains a novel RNA binding domain. This 150-amino acid region was previously found to bind preferentially to a panel of mRNAs when compared with structured RNAs, such as tRNA, U snRNA, and double-stranded RNA. The ability to broadly recognize mRNA led to the conclusion that the Nup153 RNA binding domain confers a general affinity for single-stranded RNA. Here, we have probed Nup153 RNA recognition to decipher how this unique RNA binding domain discriminates between potential targets. We first mapped the binding determinant within an RNA fragment that associates relatively robustly with the Nup153 RNA binding domain. We next designed synthetic RNA oligonucleotides to systematically delineate the features within this minimal RNA fragment that are key to Nup153 RNA-binding domain binding and demonstrated that the binding preferences of Nup153 do not reflect general preferences of an mRNA/single-stranded RNA-binding protein. We further found that the association between Nup153 and a cellular mRNA can be attributed to an interaction with specific subregions of the RNA. These results indicate that Nup153 can discriminate between mRNA and other classes of RNA transcripts due in part to direct recognition of a loose sequence motif. This information adds a new dimension to the interfaces that can contribute to recognition in mRNA export cargo selection and fate.Nuclear pore complexes are macromolecular structures that bridge the inner and outer nuclear membranes to form a channel for nucleocytoplasmic traffic (1-3). Recent molecular characterization of pore complexes has revealed that they are comprised of only ϳ30 different proteins (4, 5), with multiples of eight copies of each protein forming the 8-fold symmetric structure characteristic of the nuclear pore complex. A small number of nucleoporins are restricted in localization to either the nuclear or cytoplasmic side of the pore, and their skewed distribution contributes to distinct features on each of these faces: the nuclear basket structure and the cytoplasmic filaments. The observation that repetitive arrangement of a relatively limited number of proteins creates the elaborate pore structure suggests that each nucleoporin carries out multiple tasks, from providing structural scaffolding to contacting diverse cargo-receptor complexes as they transit through the pore.The paradigm of multifunctional pore components is well illustrated by the nucleoporin Nup153. This pore protein plays roles in both import and export pathways (6 -11). Consistent with this, Nup153 interacts with various transport receptors (7,(12)(13)(14)(15)(16)(17)(18), as well as with specific cargo (6, 10). Nup153 has also been found to be essential for the localization of other pore components (19) and is specifically thought to anchor the basket constituent TPR (20). Somewhat paradoxically, Nup153 has been shown to be dynamically localized to the nuclear pore (21,22). This apparent contradiction, as well as the multiple roles implicated for Nup153, ma...

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Distinct Functional Domains within Nucleoporins Nup153 and Nup98 Mediate Transcription-dependent Mobility

Cited by 111 publications

References 43 publications

Nup98 promotes antiviral gene expression to restrict RNA viral infection in Drosophila

Nup98 promotes antiviral gene expression to restrict RNA viral infection in Drosophila

Dynamics of the Plant Nuclear Envelope and Nuclear Pore

Sequence Preference in RNA Recognition by the Nucleoporin Nup153

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