A biallelic variant of the RNA exosome gene, EXOSC4, associated with neurodevelopmental defects impairs RNA exosome function and translation.

The RNA exosome is an evolutionarily conserved complex required for both precise RNA processing and decay. Pathogenic variants in EXOSC genes, which encode structural subunits of this complex, are linked to several autosomal recessive disorders. Here, we describe a missense allele of the EXOSC4 gene that causes a collection of clinical features in two affected siblings.

A Biallelic Variant of the RNA Exosome Gene Causes Translational Defects Associated with a Neurodevelopmental Disorder.

The RNA exosome is an evolutionarily conserved complex required for both precise RNA processing and decay. Mutations in genes encoding structural subunits of the complex are linked to several autosomal recessive disorders. Here, we describe a missense allele of the gene, which causes a collection of clinical features in two affected siblings.

Comparative analyses of disease-linked missense mutations in the RNA exosome modeled in budding yeast reveal distinct functional consequences in translation.

The RNA exosome is an evolutionarily conserved exoribonuclease complex that consists of a 3-subunit cap, a 6-subunit barrel-shaped core, and a catalytic base subunit. Missense mutations in genes encoding structural subunits of the RNA exosome cause a growing family of diseases with diverse pathologies, collectively termed RNA exosomopathies. The disease symptoms vary and can manifest as neurological defects or developmental disorders.

Histone H3 E50K mutation confers oncogenic activity and supports an EMT phenotype.

Sequencing of human patient tumors has identified recurrent missense mutations in genes encoding core histones. We report that mutations that convert histone H3 amino acid 50 from a glutamate to a lysine (H3E50K) support an oncogenic phenotype in human cells. Expression of H3E50K is sufficient to transform human cells as evidenced by a dramatic increase in cell migration and invasion, and a statistically significant increase in proliferation and clonogenicity.

Fellowship of two rings: Unprecedented insights into the structure of the yeast nuclear pore complex.

Akey et al. use complementary experimental approaches and AI-based structure prediction to reveal new details of the structure of the yeast nuclear pore complex, providing key insights into evolution, assembly, and nucleocytoplasmic transport mechanisms.