RNF10 and RIOK3 facilitate 40S ribosomal subunit degradation upon 60S biogenesis disruption or amino acid starvation

Cell Reports, Journal Year: 2025, Volume and Issue: 44(3), P. 115371 - 115371

Published: Feb. 28, 2025

Highlights•Depletion of 60S subunits or amino acid starvation activates the iRQC pathway•RNF10 expression is regulated via a translation control mechanism utilizing conserved uORFs•RNF10 acts on 40S engaged with mRNA•RIOK3 ubiquitin binding and kinase activity are required for iRQC-mediated degradationSummaryThe initiation-specific ribosome-associated quality pathway (iRQC) activated when initiation complexes fail to transition elongation-competent 80S ribosomes. Upon activation, RNF10 ubiquitylates proteins uS3 uS5, which leads decay. How in absence pharmacological inhibitors what mechanisms govern capacity remain unanswered questions. Here, we demonstrate that altering 60S:40S stoichiometry by disrupting biogenesis triggers activation Depleting critical scanning helicase eIF4A1 impairs ubiquitylation degradation, indicating mRNA engagement iRQC. We show conditions also stimulate iRQC-dependent identify RIOK3 as crucial factor interacts ubiquitylated mediate degradation. Both protein levels increase upon establishing feedforward regulates subsequent decay.Graphical abstract

Language: Английский

Ribosome-directed cancer therapies: the tip of the iceberg?

Trends in Pharmacological Sciences, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский