Nuclear speckles are key subnuclear structures that regulate gene expression in GC-rich regions. This work shows that the evolution and expansion of core speckle proteins were crucial for the increased GC content seen in amniote genomes.

Leigh syndrome is a severe and untreatable mitochondrial disease. Using patient-derived models in 2D and 3D, Zink and colleagues identify the PDE5 inhibitor sildenafil as a repurposable drug candidate, leading to lifespan extension in mammalian models and clinical improvement in six individuals with Leigh syndrome.