Nucleoplasmic Nup98 controls gene expression by regulating a DExH/D-box protein

Capitanio, Juliana S.; Montpetit, Ben; Wozniak, Richard W.

doi:10.1080/19491034.2017.1364826

Cited by 14 publications

(17 citation statements)

References 62 publications

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“…Ubiquitin-like protein ISG15 X X X DHX9 is a multifunctional ATP-dependent nucleic acid helicase that unwinds DNA and RNA in a 3= to 5= direction and is involved in many cellular processes involving RNA, such as transcriptional activation, posttranscriptional RNA regulation, splicing, mRNA translation, and RNA-mediated gene silencing (46,(51)(52)(53)(54). DHX9 has been reported to promote infectivity of various viruses, including HIV, retrovirus, influenza virus, and foot-and-mouth disease virus (FMDV).…”

Section: Discussionmentioning

confidence: 99%

Cellular RNA Helicase DHX9 Interacts with the Essential Epstein-Barr Virus (EBV) Protein SM and Restricts EBV Lytic Replication

Verma

Burton

et al. 2019

J Virol

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Epstein-Barr virus (EBV) SM protein is an RNA-binding protein that has multiple posttranscriptional gene regulatory functions essential for EBV lytic replication. In this study, we identified an interaction between SM and DHX9, a DExH-box helicase family member, by mass spectrometry and coimmunoprecipitation. DHX9 participates in many cellular pathways involving RNA, including transcription, processing, transport, and translation. DHX9 enhances virus production or infectivity of a wide variety of DNA and RNA viruses. Surprisingly, an increase in EBV late gene expression and virion production occurred upon knockdown of DHX9. To further characterize the SM-DHX9 interaction, we performed immunofluorescence microscopy of EBV-infected cells and found that DHX9 partially colocalized with SM in nuclear foci during EBV lytic replication. However, the positive effect of DHX9 depletion on EBV lytic gene expression was not confined to SM-dependent genes, indicating that the antiviral effect of DHX9 was not mediated through its effects on SM. DHX9 enhanced activation of innate antiviral pathways comprised of several interferon-stimulated genes that are active against EBV. SM inhibited the transcription-activating function of DHX9, which acts through cAMP response elements (CREs), suggesting that SM may also act to counteract DHX9’s antiviral functions during lytic replication. IMPORTANCE This study identifies an interaction between Epstein-Barr virus (EBV) SM protein and cellular helicase DHX9, exploring the roles that this interaction plays in viral infection and host defenses. Whereas most previous studies established DHX9 as a proviral factor, we demonstrate that DHX9 may act as an inhibitor of EBV virion production. DHX9 enhanced innate antiviral pathways active against EBV and was needed for maximal expression of several interferon-induced genes. We show that SM binds to and colocalizes DHX9 and may counteract the antiviral function of DHX9. These data indicate that DHX9 possesses antiviral activity and that SM may suppress the antiviral functions of DHX9 through this association. Our study presents a novel host-pathogen interaction between EBV and the host cell.

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Section: Discussionmentioning

confidence: 99%

Cellular RNA Helicase DHX9 Interacts with the Essential Epstein-Barr Virus (EBV) Protein SM and Restricts EBV Lytic Replication

Verma

Burton

et al. 2019

J Virol

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“…interactions with gene loci and the transcriptional machinery, or indirectly through their roles in regulating nuclear transport of transcriptional regulators. Some Nups are envisaged to contribute to multiple process, such as mammalian Nup98, which binds to and regulates the activity of nuclear transcription coactivators (Kasper et al, 1999) and RNA helicases (Capitanio et al, 2017(Capitanio et al, , 2018 while also functioning in nuclear transport at NPCs (Powers et al, 1997;Oka et al, 2010).…”

Section: Nups Can Influence Gene Expression By Various Mechanisms Inmentioning

confidence: 99%

Passive diffusion through nuclear pore complexes regulates levels of the yeast SAGA and SLIK coactivators complexes

Wozniak

2019

Preprint

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Nuclear pore complexes (NPCs) control gene expression by regulating the bi-directional exchange of proteins and RNAs between nuclear and cytoplasmic compartments, including access of transcriptional regulators to the nucleoplasm. Here we show that the yeast nucleoporin Nup170, in addition to binding and silencing subtelomeric genes, supports transcription of genes regulated by the SAGA transcriptional activator. Specifically, we show that less SAGA complex is bound to target genes in the absence Nup170. Consistent with this observation, levels of the SAGA complex are decreased in cells lacking Nup170, while SAGA-related SLIK complexes are increased. This change in the ratio of SAGA to SLIK complexes is due to increased nuclear activity of Pep4, a protease responsible for production of the SLIK complex. Further analyses of various nucleoporin mutants revealed that the increased nuclear entry of Pep4 observed in the nup170∆ mutant likely occurs as consequence of an increase in the sieving limits of the NPC diffusion channel. On the basis of these results, we propose that changes in passive diffusion rates represents a mechanism for regulating SAGA/SLIK complex-mediated transcriptional events.

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“…In addition to their well-established roles at NPCs, some nups moonlight in other subcellular locations, such as the nucleus (Capelson et al, 2010; Capitanio et al, 2018; Kalverda et al, 2010; Liang et al, 2013; Vaquerizas et al, 2010), or by binding the mitotic apparatus (Wozniak et al, 2010). For example, a fraction of the Nup107-160 complex is recruited to kinetochores after nuclear envelope and NPC breakdown during mitosis (Belgareh et al, 2001; Loïodice et al, 2004; Zuccolo et al, 2007), where it helps to recruit the γ-Tubulin ring complex (Mishra et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Differential turnover of Nup188 controls its levels at centrosomes and role in centriole duplication

Vishnoi

Dhanasekeran

Chalfant

et al. 2020

Journal of Cell Biology

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NUP188 encodes a scaffold component of the nuclear pore complex (NPC) and has been implicated as a congenital heart disease gene through an ill-defined function at centrioles. Here, we explore the mechanisms that physically and functionally segregate Nup188 between the pericentriolar material (PCM) and NPCs. Pulse-chase fluorescent labeling indicates that Nup188 populates centrosomes with newly synthesized protein that does not exchange with NPCs even after mitotic NPC breakdown. In addition, the steady-state levels of Nup188 are controlled by the sensitivity of the PCM pool, but not the NPC pool, to proteasomal degradation. Proximity-labeling and super-resolution microscopy show that Nup188 is vicinal to the inner core of the interphase centrosome. Consistent with this, we demonstrate direct binding between Nup188 and Cep152. We further show that Nup188 functions in centriole duplication at or upstream of Sas6 loading. Together, our data establish Nup188 as a component of PCM needed to duplicate the centriole with implications for congenital heart disease mechanisms.

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Nucleoplasmic Nup98 controls gene expression by regulating a DExH/D-box protein

Cited by 14 publications

References 62 publications

Cellular RNA Helicase DHX9 Interacts with the Essential Epstein-Barr Virus (EBV) Protein SM and Restricts EBV Lytic Replication

Cellular RNA Helicase DHX9 Interacts with the Essential Epstein-Barr Virus (EBV) Protein SM and Restricts EBV Lytic Replication

Passive diffusion through nuclear pore complexes regulates levels of the yeast SAGA and SLIK coactivators complexes

Differential turnover of Nup188 controls its levels at centrosomes and role in centriole duplication

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