bims-nucpor 2023-05-21 papers

Issue of 2023‒05‒21
three papers selected by
Sara Mingu
Johannes Gutenberg University

J Cell Sci. 2023 May 17. pii: jcs.261151. [Epub ahead of print]

Y-complex nucleoporins independently contribute to nuclear pore assembly and gene regulation in neuronal progenitors.

Clarisse Orniacki, Annalisa Verrico, Stéphane Pelletier, Benoit Souquet, Fanny Coulpier, Laurent Jourdren, Serena Benetti, Valérie Doye.

Besides assembling nuclear pore complexes, the conduits of nuclear transport, many nucleoporins also contribute to chromatin organization and gene expression, with critical roles in development and pathologies. We previously reported that Nup133 and Seh1, two components of the Y-complex subassembly of the nuclear pore scaffold, are dispensable for mouse embryonic stem cell viability but required for their survival during neuroectodermal differentiation. Here, a transcriptomic analysis revealed that Nup133 regulates a subset of genes at early stages of neuroectodermal differentiation, including Lhx1 and Nup210L, encoding a newly validated nucleoporin. These genes are also misregulated in Nup133▵Mid neuronal progenitors, in which nuclear pore basket assembly is impaired. However, a four-fold reduction of Nup133, despite also affecting basket assembly, is not sufficient to alter Nup210L and Lhx1 expression. Finally, these two genes are also misregulated in Seh1-deficient neural progenitors only showing a mild reduction in nuclear pore density. Together these data reveal a shared function of Y-complex nucleoporins in gene regulation during neuroectodermal differentiation, apparently independent of nuclear pore basket integrity.

Keywords: Lhx1; Neuronal progenitors; Nucleoporin; Nup133; Nup210L; Seh1

DOI: https://doi.org/10.1242/jcs.261151

Sci Rep. 2023 May 17. 13(1): 8035

Indel driven rapid evolution of core nuclear pore protein gene promoters.

David W J McQuarrie, Adam M Read, Frannie H S Stephens, Alberto Civetta, Matthias Soller.

Nuclear pore proteins (Nups) prominently are among the few genes linked to speciation from hybrid incompatibility in Drosophila. These studies have focused on coding sequence evolution of Nup96 and Nup160 and shown evidence of positive selection driving nucleoporin evolution. Intriguingly, channel Nup54 functionality is required for neuronal wiring underlying the female post-mating response induced by male-derived sex-peptide. A region of rapid evolution in the core promoter of Nup54 suggests a critical role for general transcriptional regulatory elements at the onset of speciation, but whether this is a general feature of Nup genes has not been determined. Consistent with findings for Nup54, additional channel Nup58 and Nup62 promoters also rapidly accumulate insertions/deletions (indels). Comprehensive examination of Nup upstream regions reveals that core Nup complex gene promoters accumulate indels rapidly. Since changes in promoters can drive changes in expression, these results indicate an evolutionary mechanism driven by indel accumulation in core Nup promoters. Compensation of such gene expression changes could lead to altered neuronal wiring, rapid fixation of traits caused by promoter changes and subsequently the rise of new species. Hence, the nuclear pore complex may act as a nexus for species-specific changes via nucleo-cytoplasmic transport regulated gene expression.

DOI: https://doi.org/10.1038/s41598-023-34985-0

Cells. 2023 04 12. pii: 1142. [Epub ahead of print]12(8):

Drosophila Models Reveal Properties of Mutant Lamins That Give Rise to Distinct Diseases.

Sydney G Walker, Christopher J Langland, Jill Viles, Laura A Hecker, Lori L Wallrath.

Mutations in the LMNA gene cause a collection of diseases known as laminopathies, including muscular dystrophies, lipodystrophies, and early-onset aging syndromes. The LMNA gene encodes A-type lamins, lamins A/C, intermediate filaments that form a meshwork underlying the inner nuclear membrane. Lamins have a conserved domain structure consisting of a head, coiled-coil rod, and C-terminal tail domain possessing an Ig-like fold. This study identified differences between two mutant lamins that cause distinct clinical diseases. One of the LMNA mutations encodes lamin A/C p.R527P and the other codes lamin A/C p.R482W, which are typically associated with muscular dystrophy and lipodystrophy, respectively. To determine how these mutations differentially affect muscle, we generated the equivalent mutations in the Drosophila Lamin C (LamC) gene, an orthologue of human LMNA. The muscle-specific expression of the R527P equivalent showed cytoplasmic aggregation of LamC, a reduced larval muscle size, decreased larval motility, and cardiac defects resulting in a reduced adult lifespan. By contrast, the muscle-specific expression of the R482W equivalent caused an abnormal nuclear shape without a change in larval muscle size, larval motility, and adult lifespan compared to controls. Collectively, these studies identified fundamental differences in the properties of mutant lamins that cause clinically distinct phenotypes, providing insights into disease mechanisms.

Keywords: Drosophila; Dunnigan type; Emery–Dreifuss muscular dystrophy; cardiomyopathy; familial partial lipodystrophy; intermediate filaments; laminopathy; lamins; nuclear envelope; nuclear pore

DOI: https://doi.org/10.3390/cells12081142