Senescent Cells Differentially Translate Senescence-Related mRNAs Via Ribosome Heterogeneity

Abstract

The ribosome has a lateral stalk which consists of rpLP0, rpLP1, and rpLP2. One of these proteins, rpLP2, is decreased in translating ribosome when cellular senescence is induced. Y-box binding protein-1 (YB-1) is also reduced in polysomal fraction of senescent cells. We discovered that rpLP2 depletion in the ribosome can cause the detachment of YB-1 in polysomes and that it is linked to cellular senescence. Our results also revealed that a decrement of CK2 alpha or GRK2 in senescent cells induced an increment of unphosphorylated rpLP2, resulting in release of YB-i from polysomes. This heterogeneous senescent ribosome has different translational efficiencies for some senescence-related genes. We also showed that the decrease of rpLP1/rpLP2 and YB-1 in senescent ribosomes was not specific to cell type or stress type and the same phenomenon was also observed in aged mouse livers regardless of gender. Taken together, our results suggest that the senescent ribosome complex appears to have low levels of rpLP1/rpLP2 and YB-1, resulting in altered translational efficiency for senescence-related genes.