Ribosomopathy-associated mutations cause proteotoxic stress that is alleviated by TOR inhibition.

ABSTRACT: Ribosomes are multicomponent molecular machines that synthesize all of the proteins of living cells. Most of the genes that encode the protein components of ribosomes are therefore essential. A reduction in gene dosage is often viable albeit deleterious and is associated with human syndromes, which are collectively known as ribosomopathies^1-3. The cell biological basis of these pathologies has remained unclear. Here, we model human ribosomopathies in Drosophila and find widespread apoptosis and cellular stress in the resulting animals. This is not caused by insufficient protein synthesis, as reasonably expected. Instead, ribosomal protein deficiency elicits proteotoxic stress, which we suggest is caused by the accumulation of misfolded proteins that overwhelm the protein degrada

SUBMITTER: Recasens-Alvarez C 

PROVIDER: S-EPMC7116740 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature