Dissociation of the nuclear basket triggers chromosome loss in aging yeast

In many organisms, aging is a clear risk factor for increased rates of chromosome mis-segregation, the main source of aneuploidy. Here, we report that old yeast mother cells lose chromosomes by partitioning them asymmetrically to their daughter cells together with the pre-existing (old) Sindle Pole Body (centrosome equivalent in yeast). Strikingly, remodelling of the NPC and the displacement of its nuclear basket triggered these asymmetric segregation events. Concomitantly, basket displacement also caused unspliced pre-mRNAs to leak to the cytoplasm. We show that removing the introns of three genes involved in chromosome segregation was sufficient to fully suppress chromosome loss in old cells. Furthermore, promoting pre-mRNA leakage in young cells also caused asymmetric chromosome partition and loss through the same three introns. Therefore, we propose that basket displacement from NPCs and its ensuing effects on pre-mRNA quality control are a key trigger of aging phenotypes such as aneuploidy.