bims-nucpor 2023-07-02 papers

on Nuclear pore complex and nucleoporins in stress, aging and disease

Issue of 2023–07–02
two papers selected by
Sara Mingu, Johannes Gutenberg University

The HIV-1 capsid core is an opportunistic nuclear import receptor.
Nuclear pore complexes mediate subtelomeric gene silencing by regulating PCNA levels on chromatin.

Nat Commun. 2023 Jun 24. 14(1): 3782

The HIV-1 capsid core is an opportunistic nuclear import receptor.

Guangai Xue, Hyun Jae Yu, Cindy Buffone, Szu-Wei Huang, KyeongEun Lee, Shih Lin Goh, Anna T Gres, Mehmet Hakan Guney, Stefan G Sarafianos, Jeremy Luban, Felipe Diaz-Griffero, Vineet N KewalRamani.

The movement of viruses and other large macromolecular cargo through nuclear pore complexes (NPCs) is poorly understood. The human immunodeficiency virus type 1 (HIV-1) provides an attractive model to interrogate this process. HIV-1 capsid (CA), the chief structural component of the viral core, is a critical determinant in nuclear transport of the virus. HIV-1 interactions with NPCs are dependent on CA, which makes direct contact with nucleoporins (Nups). Here we identify Nup35, Nup153, and POM121 to coordinately support HIV-1 nuclear entry. For Nup35 and POM121, this dependence was dependent cyclophilin A (CypA) interaction with CA. Mutation of CA or removal of soluble host factors changed the interaction with the NPC. Nup35 and POM121 make direct interactions with HIV-1 CA via regions containing phenylalanine glycine motifs (FG-motifs). Collectively, these findings provide additional evidence that the HIV-1 CA core functions as a macromolecular nuclear transport receptor (NTR) that exploits soluble host factors to modulate NPC requirements during nuclear invasion.

DOI: https://doi.org/10.1038/s41467-023-39146-5
J Cell Biol. 2023 09 04. pii: e202207060. [Epub ahead of print]222(9):

Nuclear pore complexes mediate subtelomeric gene silencing by regulating PCNA levels on chromatin.

Sanjeev Kumar, Maxwell L Neal, Song Li, Arti T Navare, Trevor Van Eeuwen, Richard W Wozniak, Fred D Mast, Michael P Rout, John D Aitchison.

The nuclear pore complex (NPC) physically interacts with chromatin and regulates gene expression. The Saccharomyces cerevisiae inner ring nucleoporin Nup170 has been implicated in chromatin organization and the maintenance of gene silencing in subtelomeric regions. To gain insight into how Nup170 regulates this process, we used protein-protein interactions, genetic interactions, and transcriptome correlation analyses to identify the Ctf18-RFC complex, an alternative proliferating cell nuclear antigen (PCNA) loader, as a facilitator of the gene regulatory functions of Nup170. The Ctf18-RFC complex is recruited to a subpopulation of NPCs that lack the nuclear basket proteins Mlp1 and Mlp2. In the absence of Nup170, PCNA levels on DNA are reduced, resulting in the loss of silencing of subtelomeric genes. Increasing PCNA levels on DNA by removing Elg1, which is required for PCNA unloading, rescues subtelomeric silencing defects in nup170Δ. The NPC, therefore, mediates subtelomeric gene silencing by regulating PCNA levels on DNA.

DOI: https://doi.org/10.1083/jcb.202207060