Nuclear transport

  • Article
    | Open Access

    The permeability barrier of nuclear pore complexes blocks passage of inert macromolecules but allows rapid, receptor-mediated, and RanGTPase-driven transport of cargoes up to ribosome size. The authors now show that such a barrier can be faithfully recapitulated by an ultimately simplified FG phase assembled solely from a tandemly repeated 12mer GLFG peptide.

    • Sheung Chun Ng
    • , Thomas Güttler
    •  & Dirk Görlich
  • Article
    | Open Access

    New contractile units are required during cardiac hypertrophy, though it remains unclear precisely where and how these new sarcomeres are added. Here the authors reveal that in the heart, microtubules spatiotemporally regulate mRNAs and ribosomes to build new sarcomeres, a role which is essential for growth.

    • Emily A. Scarborough
    • , Keita Uchida
    •  & Benjamin L. Prosser
  • Article
    | Open Access

    The SOX2 pioneer transcription factor performs critical roles in pluripotency and self-renewal of embryonic stem cells. Here the authors show that SOX2’s two nuclear localization signal sequences form a contiguous binding interface on the nuclear import receptor importin-α3, and provide a structural basis for the preference of SOX2 binding to IMPα3.

    • Bikshapathi Jagga
    • , Megan Edwards
    •  & Jade K. Forwood
  • Article
    | Open Access

    The Y complex is an essential component of the nuclear pore complex but a full model based on experimental structures is lacking. Here, the authors complete the model of the yeast Y complex with two nanobody-bound crystal structures, providing molecular insights into its flexibility and membrane anchoring.

    • Sarah A. Nordeen
    • , Daniel L. Turman
    •  & Thomas U. Schwartz
  • Article
    | Open Access

    The transcriptional regulator YAP shuttles rapidly between the cytoplasm and nucleus, but whether and how dynamics such as amplitude and frequency affect target gene transcription is unclear. Here, using live imaging of endogenous YAP and target-gene transcription, the authors show that YAP-dependent signalling is encoded through rapid and concerted changes in the nucleo-cytoplasmic distribution of YAP.

    • J. Matthew Franklin
    • , Rajarshi P. Ghosh
    •  & Jan T. Liphardt
  • Article
    | Open Access

    mRNAs export from the nucleus is thought to be regulated in part by three nucleoporins that comprise the nuclear basket, but whether and how distinct basket nucleoporins interact with the RNA export machinery is unclear. Here, the authors use rapid auxin-mediated degradation of basket nucleoporins Nup153, Nup50, and Tpr, and see that Tpr interacts with the TREX-2 mRNA export complex.

    • Vasilisa Aksenova
    • , Alexandra Smith
    •  & Mary Dasso
  • Article
    | Open Access

    The contribution of central and peripheral channels of nuclear pores to transport of transmembrane proteins is unclear. Here the authors show that most inner nuclear membrane proteins use only peripheral channels, but some extend nuclear localization signals into the central channel for directed nuclear transport.

    • Krishna C. Mudumbi
    • , Rafal Czapiewski
    •  & Weidong Yang
  • Article
    | Open Access

    Fluorogenic RNA aptamers have been used for RNA imaging, but folding and fluorescence stability often limited their use in high resolution applications. Here the authors present an array of stably folding Mango II aptamers for imaging of coding and non-coding RNAs at single-molecule resolution, in both live and fixed cells.

    • Adam D. Cawte
    • , Peter J. Unrau
    •  & David S. Rueda
  • Article
    | Open Access

    Golgi disassembly is required for mitosis and occurs by vesicle fusion suppression, although the mechanism is unclear. Here, Chang et al. show, with quantitative analyses and crystallography, that Importin-α regulates this process by blocking GM130-p115 interactions in a Ran pathway-independent way.

    • Chih-Chia Chang
    • , Ching-Jou Chen
    •  & Kuo-Chiang Hsia
  • Article
    | Open Access

    The nuclear pore complex (NPC) is known to regulate p53 signaling and this has mainly been linked to peripheral NPC subunits. Here the authors show that Nup155 from the NPC inner ring regulates the p53 pathway by controlling p21 translation while also being a target of p53-mediated repression.

    • Kerstin Holzer
    • , Alessandro Ori
    •  & Stephan Singer
  • Article
    | Open Access

    Large protein complexes and ribonucleoprotein particles (RNPs) such as pre-ribosomes are transported from the nucleus to the cytoplasm through the nuclear pore complex (NPC). Here the authors use ultrafast freezing and electron tomography to catch snapshots of native RNPs crossing the NPC and estimate their transit time using a probabilistic model.

    • Franck Delavoie
    • , Vanessa Soldan
    •  & Pierre-Emmanuel Gleizes
  • Article
    | Open Access

    The transcriptional co-factors Yap and TAZ are regulated by Hippo signalling and mechanical forces via their nucleocytoplasmic shuttling. Here the authors identify a RhoA-regulated C-terminal nuclear localization signal and a TEAD-regulated N-terminal nuclear export signal of TAZ in an epithelial cell line.

    • Michael Kofler
    • , Pam Speight
    •  & András Kapus
  • Article
    | Open Access

    Importin α isoforms regulate the nuclear import of different cargo proteins but the mechanisms conferring isoform specificity are not fully understood. Here, the authors study the interactions of importin α1 and α3 with two viral cargos, elucidating the structural basis for isoform-specific cargo recognition.

    • Kate M. Smith
    • , Sofiya Tsimbalyuk
    •  & Jade K. Forwood
  • Article
    | Open Access

    On amino acid deprivation TFEB translocates from the cytoplasm to the nucleus. Here the authors identify a nuclear export signal in TFEB that is recognized by the exportin CRM1, and show that dual phosphorylation at S142 and S138 by mTOR accelerates export of TFEB.

    • Gennaro Napolitano
    • , Alessandra Esposito
    •  & Andrea Ballabio
  • Article
    | Open Access

    While the architecture of vertebrate nuclear pore complexes (NPCs) is well understood, the extent of its evolutionary conservation is still unclear. Here, the authors analyze the in situ architecture of an algal NPC, revealing distinct structural features that provide insights into NPC evolution.

    • Shyamal Mosalaganti
    • , Jan Kosinski
    •  & Martin Beck
  • Article
    | Open Access

    The export of mRNA to the cytosol depends on the nuclear pore complex (NPC) and the activation of the helicase DDX19, but their interplay in humans remains poorly understood. Here, the authors present a structural and functional analysis of DDX19 activation, revealing how the human NPC regulates mRNA export.

    • Daniel H. Lin
    • , Ana R. Correia
    •  & André Hoelz
  • Article
    | Open Access

    MxB is an interferon-induced GTPase that inhibits HIV replication. Here, Crameri et al. show that MxB restricts replication of herpesviruses by inhibiting delivery of incoming viral DNA into the nucleus, and this antiviral activity depends on MxB’s GTPase activity.

    • Michel Crameri
    • , Michael Bauer
    •  & Jovan Pavlovic
  • Article
    | Open Access

    The nuclear pore complex is crucial for mediating nucleocytoplasmic exchanges. Here the authors use budding yeast to reveal a mechanism responsible of maintaining nucleoporin homeostasis by sensing changes in the complex integrity and further altering the metabolism of the corresponding mRNAs.

    • Jérôme O. Rouvière
    • , Manuel Bulfoni
    •  & Benoit Palancade
  • Article
    | Open Access

    The proteome-wide characterization of proteostasis depends on robust approaches to determine protein half-lives. Here, the authors improve the accuracy and precision of mass spectrometry-based quantification, enabling reliable protein half-life determination in several non-dividing cell types.

    • Toby Mathieson
    • , Holger Franken
    •  & Mikhail M. Savitski
  • Article
    | Open Access

    Drosophila Polo kinase is the founding member of the Polo-Like Kinase (PLK) family and a master regulator of mitosis and cytokinesis. Here the authors uncover a molecular mechanism for the spatiotemporal regulation of Polo kinase during mitotic entry through a phosphorylation event that triggers nuclear import.

    • David Kachaner
    • , Damien Garrido
    •  & Vincent Archambault
  • Article
    | Open Access

    Single cells can display large heterogeneity in gene induction. Here, Aymoz et al. present an expression reporter based on protein translocation that can accurately measure both the levels and dynamics of protein synthesis in live single cells with a temporal resolution of less than one minute.

    • Delphine Aymoz
    • , Victoria Wosika
    •  & Serge Pelet
  • Article
    | Open Access

    Light-inducible control of protein subcellular localization holds great promise for synthetic biology applications and insights into basic cell biology. Here the authors develop a genetically-encoded light-inducible nuclear export system and apply it to a synthetic repressor and p53 transcriptional activity.

    • Dominik Niopek
    • , Pierre Wehler
    •  & Barbara Di Ventura
  • Article
    | Open Access

    While ERK signalling can produce switch-like cell behaviour, phosphorylation of ERK increases linearly with extracellular signals. Here, the authors solve this seeming contradiction by showing that nuclear translocation of ERK behaves in a switch-like manner and is controlled by ERK activity.

    • Yuki Shindo
    • , Kazunari Iwamoto
    •  & Koichi Takahashi
  • Article
    | Open Access

    Measuring single-cell mRNA dynamics is critical to understand gene expression. Here, using RNA Spinach technique to detect very low abundant mRNAs, Guet et al. report an analysis of the osmotic shock response in live yeast by localizing induced transcription factors, target gene loci and corresponding transcripts.

    • David Guet
    • , Laura T. Burns
    •  & Catherine Dargemont
  • Article
    | Open Access

    Endocytosis typically directs proteins on a recycling route back to the plasma membrane, transport to the Golgi apparatus or delivery to the lysosome. Here Chaumet et al.describe a population of vesicles that can fuse directly with the outer nuclear membrane and deliver cargo into the nuclear envelope, where it can be translocated into the nucleoplasm.

    • Alexandre Chaumet
    • , Graham D. Wright
    •  & Frederic Bard
  • Article
    | Open Access

    Nuclear pore complexes (NPCs) are large macromolecular assemblies that mediate the exchange of molecules between the nucleus and cytoplasm. Here the authors present a 20 Å cryo-EM structure of the X. laevisNPC in different states of transport to propose a model for the architecture of the NPC’s molecular gate within its central channel.

    • Matthias Eibauer
    • , Mauro Pellanda
    •  & Ohad Medalia
  • Article
    | Open Access

    Eukaryotic ribosomal proteins contain nuclear localization signals (NLSs) that their bacterial counterparts lack. Here the authors compare homologous proteins from bacterial and eukaryotic ribosomes to show how NLSs could emerge in the course of evolution, and use this knowledge to identify novel NLSs.

    • Sergey Melnikov
    • , Adam Ben-Shem
    •  & Marat Yusupov
  • Article
    | Open Access

    Biogenesis of the 80S ribosome involves more than 200 pre-ribosomal factors, which ensure the sequential assembly of ribosomal proteins and RNAs. Here the authors show that the nuclear transport adaptor Syo1 shields the 5S RNP-docking site on RpL11 before incorporation into the pre-60S through molecular mimicry.

    • Fabiola R. Calviño
    • , Satyavati Kharde
    •  & Irmgard Sinning
  • Article |

    The extracellular signal-regulated kinase 1/2 (ERK1/2) cascade is involved in the induction and maintenance of cancers. Here the authors design an ERK-derived peptide that blocks ERK nuclear import, thus proposing a novel approach to treat tumours with mutational activation of the ERK pathway.

    • Alexander Plotnikov
    • , Karen Flores
    •  & Rony Seger
  • Article
    | Open Access

    Heat shock induces proteotoxic stress, and the cellular response is mediated by heat-shock factor 1 (HSF1). Here, Tan et al.show that following heat shock, mitochondrial SSBP1 translocates to the nucleus and binds HSF1 to enhance the expression of chaperones and support the maintenance of mitochondrial function.

    • Ke Tan
    • , Mitsuaki Fujimoto
    •  & Akira Nakai
  • Article
    | Open Access

    Retroviruses such as HIV integrate into the host genome as an essential step prior to their replication. Here Lelek et al. identify nuclear pore complex proteins that are essential for HIV nuclear import and productive integration, and show that the intranuclear protein Tpr influences integration into transcriptionally active chromatin.

    • Mickaël Lelek
    • , Nicoletta Casartelli
    •  & Francesca Di Nunzio
  • Article
    | Open Access

    TFIID is an essential transcription factor complex that controls the expression of most protein-coding genes in eukaryotes. Here the authors identify and characterize a complex containing TAF2, TAF8 and TAF10, which assembles in the cytoplasm before integration into the nuclear holo–TFIID complex.

    • Simon Trowitzsch
    • , Cristina Viola
    •  & Imre Berger
  • Article
    | Open Access

    Nuclear import of transcriptional regulators and export of mRNA are essential steps for the manufacture of proteins in the cytoplasm. Here, Rajakylä et al.link these two activities by showing that the mRNA export factor Ddx19 promotes the nuclear import of the transcriptional coactivator MKL1.

    • Eeva Kaisa Rajakylä
    • , Tiina Viita
    •  & Maria K. Vartiainen
  • Article
    | Open Access

    The human Holliday junction resolvase GEN1 functions during anaphase to eliminate recombination intermediates that block proper chromosome segregation. Here, the authors demonstrate that GEN1 activity is regulated independently of its phosphorylation status and relies on its active exclusion from the nucleus.

    • Ying Wai Chan
    •  & Stephen C. West
  • Article |

    Messenger RNAs and their associated proteins are transported from the nucleus through highly selective nuclear pore complexes. Using ultrahigh resolution single-molecule imaging, the authors visualise the path taken by each messenger RNA as it negotiates the pore’s selectivity filter.

    • Jiong Ma
    • , Zhen Liu
    •  & Weidong Yang
  • Article |

    Zonal occludens and claudin form tight junctions near the apical surface of cells and are important in polarized epithelia. In this study, the translational regulatory sequence-specific RNA binding protein CPEB is shown to be required for the correct localization of zona occluden 1 mRNA in mammary epithelial cells.

    • Kentaro Nagaoka
    • , Tsuyoshi Udagawa
    •  & Joel D. Richter