Cargo transport through the nuclear pore complex at a glance

Paci, Giulia; Caria, Joana; Lemke, Edward A.

doi:10.1242/jcs.247874

Cited by 62 publications

(44 citation statements)

References 130 publications

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“…Finally, a cylindrical basket extends from the nuclear side and in concert with a cytoplasmic platform comprised of the Nup82 complex, forms a pipeline for RNA processing and export (9,10). The arrangement of proteins, termed FG Nups, within the cylindrical scaffold creates an array of anchor points for intrinsically disordered Phe-Gly (FG) repeat domains that project inwards to form the central transport path (7,11); these FG domains provide binding sites for the bi-directional, facilitated diffusion of nuclear transport factors with their macromolecular cargos (12)(13)(14) To better understand NPC function, positional information for yeast Nups was determined by integrative modeling with biochemical and physical restraints to create a "nearestneighbor" map (15). In subsequent work, human (16)(17)(18) and algal (19).…”

Section: Introductionmentioning

confidence: 99%

Comprehensive Structure and Functional Adaptations of the Yeast Nuclear Pore Complex

Akey

Singh

Ouch

et al. 2021

Preprint

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Nuclear Pore Complexes (NPCs) mediate the nucleocytoplasmic transport of macromolecules. Here we provide a structure of the yeast NPC in which the inner ring is resolved by cryo-EM at - helical resolution to show how flexible connectors tie together different structural and functional layers in the spoke. These connectors are targets for phosphorylation and regulated disassembly in cells with an open mitosis. Moreover, some nucleoporin pairs and karyopherins have similar interaction motifs, which suggests an evolutionary and mechanistic link between assembly and transport. We also provide evidence for three major NPC variants that foreshadow functional specializations at the nuclear periphery. Cryo-electron tomography extended these studies to provide a comprehensive model of the in situ NPC with a radially-expanded inner ring. Our model reveals novel features of the central transporter and nuclear basket, suggests a role for the lumenal ring in restricting dilation and highlights the structural plasticity required for transport by the NPC.

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Section: Introductionmentioning

confidence: 99%

Comprehensive Structure and Functional Adaptations of the Yeast Nuclear Pore Complex

Akey

Singh

Ouch

et al. 2021

Preprint

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“…They control the flux of molecules across the nuclear envelope, consisting of an outer and inner nuclear membrane, and accordingly establish the identity of the nucleus and cytoplasm as distinct compartments. While metabolites and ions freely diffuse through NPCs, the passage of larger molecules is constrained by their size and surface properties [ 1 ]. In contrast, selective nuclear import and export of macromolecules such as most proteins and RNA-protein complexes require transport signals.…”

Section: Introductionmentioning

confidence: 99%

Dunking into the Lipid Bilayer: How Direct Membrane Binding of Nucleoporins Can Contribute to Nuclear Pore Complex Structure and Assembly

Hamed

Antonin

2021

Cells

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Nuclear pore complexes (NPCs) mediate the selective and highly efficient transport between the cytoplasm and the nucleus. They are embedded in the two membrane structure of the nuclear envelope at sites where these two membranes are fused to pores. A few transmembrane proteins are an integral part of NPCs and thought to anchor these complexes in the nuclear envelope. In addition, a number of nucleoporins without membrane spanning domains interact with the pore membrane. Here we review our current knowledge of how these proteins interact with the membrane and how this interaction can contribute to NPC assembly, stability and function as well as shaping of the pore membrane.

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“…They are recruited to the mRNA during processing and bind export factors depending on proper execution of the processing steps. Binding of export factors along the transcript is crucial for export as they coat the highly-charged mRNA and interact with the hydrophobic meshwork of phenylalanine-glycine (FG) nucleoporins in the interior of the NPC, allowing efficient passage of the messenger ribonucleoprotein (mRNP) [26,27]. In higher eukaryotes, splicing is often marked by the binding of an exon junction complex (EJC) upstream of the exonexon junction [28].…”

Section: Quality Control Of Splicing In the Nucleus-retention Or Export Of Mrnamentioning

confidence: 99%

Nuclear mRNA Quality Control and Cytoplasmic NMD Are Linked by the Guard Proteins Gbp2 and Hrb1

Krebber

2021

IJMS

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Pre-mRNA splicing is critical for cells, as defects in this process can lead to altered open reading frames and defective proteins, potentially causing neurodegenerative diseases and cancer. Introns are removed in the nucleus and splicing is documented by the addition of exon-junction-complexes (EJCs) at exon-exon boundaries. This “memory” of splicing events is important for the ribosome, which translates the RNAs in the cytoplasm. In case a stop codon was detected before an EJC, translation is blocked and the RNA is eliminated by the nonsense-mediated decay (NMD). In the model organism Saccharomyces cerevisiae, two guard proteins, Gbp2 and Hrb1, have been identified as nuclear quality control factors for splicing. In their absence, intron-containing mRNAs leak into the cytoplasm. Their presence retains transcripts until the process is completed and they release the mRNAs by recruitment of the export factor Mex67. On transcripts that experience splicing problems, these guard proteins recruit the nuclear RNA degradation machinery. Interestingly, they continue their quality control function on exported transcripts. They support NMD by inhibiting translation and recruiting the cytoplasmic degradation factors. In this way, they link the nuclear and cytoplasmic quality control systems. These discoveries are also intriguing for humans, as homologues of these guard proteins are present also in multicellular organisms. Here, we provide an overview of the quality control mechanisms of pre-mRNA splicing, and present Gbp2 and Hrb1, as well as their human counterparts, as important players in these pathways.

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Cargo transport through the nuclear pore complex at a glance

Cited by 62 publications

References 130 publications

Comprehensive Structure and Functional Adaptations of the Yeast Nuclear Pore Complex

Comprehensive Structure and Functional Adaptations of the Yeast Nuclear Pore Complex

Dunking into the Lipid Bilayer: How Direct Membrane Binding of Nucleoporins Can Contribute to Nuclear Pore Complex Structure and Assembly

Nuclear mRNA Quality Control and Cytoplasmic NMD Are Linked by the Guard Proteins Gbp2 and Hrb1

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