Author Response: The Molecular Basis for ANE Syndrome Revealed by the Large Ribosomal Subunit Processome Interactome

The study explored the molecular basis of ANE syndrome, a ribosomopathy linked to a mutation in the RBM28 protein, using yeast as a model. The mutation, a leucine to proline substitution, disrupted the function of Nop4, the yeast equivalent of RBM28, leading to growth defects and pre-rRNA processing issues. This mutation altered protein folding, affecting crucial protein-protein interactions necessary for ribosome assembly. The research, which included a study of 5 boys from the same family, concluded that defective protein folding due to the mutation was a key factor in ANE syndrome pathogenesis. The study also found that the RNA recognition motifs (RRMs) 3 and 4 of Nop4 were essential for maintaining these interactions and could complement growth defects caused by Nop4 depletion at certain temperatures.