bims-nucpor 2021-10-10 papers

Issue of 2021–10–10
three papers selected by
Sara Mingu, Johannes Gutenberg University

Wiley Interdiscip Rev RNA. 2021 Nov;12(6): e1660

Choosing the right exit: How functional plasticity of the nuclear pore drives selective and efficient mRNA export.

Pierre Bensidoun, Daniel Zenklusen, Marlene Oeffinger.

The nuclear pore complex (NPC) serves as a central gate for mRNAs to transit from the nucleus to the cytoplasm. The ability for mRNAs to get exported is linked to various upstream nuclear processes including co-transcriptional RNP assembly and processing, and only export competent mRNPs are thought to get access to the NPC. While the nuclear pore is generally viewed as a monolithic structure that serves as a mediator of transport driven by transport receptors, more recent evidence suggests that the NPC might be more heterogenous than previously believed, both in its composition or in the selective treatment of cargo that seek access to the pore, providing functional plasticity to mRNA export. In this review, we consider the interconnected processes of nuclear mRNA metabolism that contribute and mediate export competence. Furthermore, we examine different aspects of NPC heterogeneity, including the role of the nuclear basket and its associated complexes in regulating selective and/or efficient binding to and transport through the pore. This article is categorized under: RNA Export and Localization > Nuclear Export/Import RNA Turnover and Surveillance > Turnover/Surveillance Mechanisms RNA Interactions with Proteins and Other Molecules > Protein-RNA Interactions: Functional Implications.

Keywords: Mlp1; NPC heterogeneity; TPR; TREX-2; export competency; export efficiency; export selectivity; gene gating; kinetic proofreading; mRNA export; nuclear basket; nuclear organization; nuclear pore complex; nuclear retention

DOI: https://doi.org/10.1002/wrna.1660

Traffic. 2021 Oct 08.

Implication of the nuclear trafficking of rabies virus P3 protein in viral pathogenicity.

Aaron M Brice, Ericka Watts, Bevan Hirst, David A Jans, Naoto Ito, Gregory W Moseley.

Although the majority of viruses of the family Mononegvirales replicate exclusively in the host cell cytoplasm, many of these viruses encode proteins that traffic between the nucleus and cytoplasm, which is believed to enable accessory functions in modulating the biology of the infected host cell. Among these, the P3 protein of rabies virus localizes to the nucleus through the activity of several specific nuclear localization and nuclear export signals. The major defined functions of P3 are in evasion of interferon (IFN)-mediated antiviral responses, including through inhibition of DNA-binding by IFN-activated STAT1. P3 also localizes to nucleoli and PML nuclear bodies, and interacts with nucleolin and PML, indicative of several intranuclear roles. The relationship of P3 nuclear localization with pathogenicity, however, is unresolved. We report that nucleocytoplasmic localisation of P3 proteins from a pathogenic RABV strain, Nishigahara (Ni), and non-pathogenic Ni-derived strain, Ni-CE, differs significantly, with nuclear accumulation defective for Ni-CE-P3. Molecular mapping indicates that altered localization derives from a coordinated effect, including two residue substitutions that independently disable nuclear localization and augment nuclear export signals, collectively promoting nuclear exclusion. Intriguingly, this appears to relate to effects on protein conformation or regulatory mechanisms, rather than direct modification of defined trafficking signal sequences. These data provide new insights into the role of regulated nuclear trafficking of a viral protein in the pathogenicity of a virus that replicates in the cytoplasm.

Keywords: cell nucleus; lyssavirus; nuclear export signal; nuclear localization signal; nuclear transport; pathogenicity; phosphoprotein; rabies virus; virus-host interactions

DOI: https://doi.org/10.1111/tra.12821

Nat Commun. 2021 Oct 08. 12(1): 5904

Nuclear transporter Importin-13 plays a key role in the oxidative stress transcriptional response.

K A Gajewska, H Lescesen, M Ramialison, K M Wagstaff, D A Jans.

The importin superfamily member Importin-13 is a bidirectional nuclear transporter. To delineate its functional roles, we performed transcriptomic analysis on wild-type and Importin-13-knockout mouse embryonic stem cells, revealing enrichment of differentially expressed genes involved in stress responses and apoptosis regulation. De novo promoter motif analysis on 277 Importin-13-dependent genes responsive to oxidative stress revealed an enrichment of motifs aligned to consensus sites for the transcription factors specificity protein 1, SP1, or Kruppel like factor 4, KLF4. Analysis of embryonic stem cells subjected to oxidative stress revealed that Importin-13-knockout cells were more resistant, with knockdown of SP1 or KLF4 helping protect wild-type embryonic stem cells against stress-induced death. Importin-13 was revealed to bind to SP1 and KLF4 in a cellular context, with a key role in oxidative stress-dependent nuclear export of both transcription factors. The results are integral to understanding stress biology, highlighting the importance of Importin-13 in the stress response.

DOI: https://doi.org/10.1038/s41467-021-26125-x