bims-nucpor 2022-08-07 papers

Issue of 2022–08–07
three papers selected by
Sara Mingu, Johannes Gutenberg University

Brief Funct Genomics. 2022 Aug 03. pii: elac022. [Epub ahead of print]

Tau-FG-nucleoporin98 interaction and impaired nucleocytoplasmic transport in Alzheimer's disease.

An emerging pathophysiology associated with the neurodegenerative Alzheimer's disease (AD) is the impairment of nucleocytoplasmic transport (NCT). The impairment can originate from damage to the nuclear pore complex (NPC) or other factors involved in NCT. The phenylalanine-glycine nucleoporins (FG-Nups) form a crucial component of the NPC, which is central to NCT. Recent discoveries have highlighted that the neuropathological protein tau is involved in direct interactions with the FG-Nups and impairment of the NCT process. Targeting such interactions may lead to the identification of novel interaction inhibitors and offer new therapeutic alternatives for the treatment of AD. This review highlights recent findings associated with impaired NCT in AD and the interaction between tau and the FG-Nups.

Keywords: FG-Nup98; hyperphosphorylated tau; neurodegeneration; nuclear membrane; nuclear pore complex; protein–protein interaction

DOI: https://doi.org/10.1093/bfgp/elac022

Curr Opin Virol. 2022 Jul 28. pii: S1879-6257(22)00065-7. [Epub ahead of print]55 101254

Viral-host interactions during splicing and nuclear export of influenza virus mRNAs.

Matthew Esparza, Prasanna Bhat, Beatriz Ma Fontoura.

As influenza-A viruses (IAV) replicate in the host cell nucleus, intranuclear pathways are usurped for viral gene expression. The eight genomic viral ribonucleoproteins (vRNPs) segments of IAV are transcribed and two generate viral mRNAs (M and NS) that undergo alternative splicing followed by export from the nucleus. The focus of this review is on viral RNA splicing and nuclear export. Recent mechanistic advances on M and NS splicing show differential regulation by RNA-binding proteins as well as distinct intranuclear localization. After a review of IAV splicing, we will discuss the nuclear export of viral mRNAs, which occur by interacting with specific constituents of the host mRNA export machinery that translocate viral mRNAs through the nuclear pore complex for translation in the cytoplasm.

DOI: https://doi.org/10.1016/j.coviro.2022.101254

Front Cell Dev Biol. 2022 ;10 931237

Nuclear Localization Signals for Optimization of Genetically Encoded Tools in Neurons.

Maksim M Karasev, Mikhail Baloban, Vladislav V Verkhusha, Daria M Shcherbakova.

Nuclear transport in neurons differs from that in non-neuronal cells. Here we developed a non-opsin optogenetic tool (OT) for the nuclear export of a protein of interest induced by near-infrared (NIR) light. In darkness, nuclear import reverses the OT action. We used this tool for comparative analysis of nuclear transport dynamics mediated by nuclear localization signals (NLSs) with different importin specificities. We found that widely used KPNA2-binding NLSs, such as Myc and SV40, are suboptimal in neurons. We identified uncommon NLSs mediating fast nuclear import and demonstrated that the performance of the OT for nuclear export can be adjusted by varying NLSs. Using these NLSs, we optimized the NIR OT for light-controlled gene expression for lower background and higher contrast in neurons. The selected NLSs binding importins abundant in neurons could improve performance of genetically encoded tools in these cells, including OTs and gene-editing tools.

Keywords: importins; near-infrared; neurons; nuclear localization signal; nuclear transport; optogenetic tools

DOI: https://doi.org/10.3389/fcell.2022.931237