Nucleocytoplasmic Communication in Progeria

Hutchinson Gilford Progeria Syndrome (HGPS) was linked to a mutation in the lamin A gene, resulting in the production of progerin, which altered nuclear lamina structure and affected nuclear morphology and gene expression. This study proposed an alternative mechanism where changes in chromatin, due to progerin, affected the functions of RCC1 and Ran, crucial for nuclear transport. Mislocalization of Ran in HGPS patient fibroblasts was observed, affecting the import of large nuclear cargo, such as nucleoporin Tpr and proteins involved in DNA repair and transcription. The study also explored the relationship between nuclear lamina disruption, Ran system, and oxidative stress, suggesting that Ran system disruption might be an early event in the pathway leading to Progeria phenotypes. This work provided a new perspective on Progeria, proposing that defective nuclear transport could cause global gene expression changes in the disease.