EIF3 mRNA selectivity profiling reveals eIF3k as a cancer-relevant regulator of ribosome content

ABSTRACT: eIF3, whose subunits are frequently overexpressed in cancer, regulates mRNA translation from initiation to termination, but mRNA-selective functions of individual subunits remain poorly defined. Using multi-omic profiling upon acute depletion of eIF3 subunits, we observed that while eIF3a, b, e, and f markedly differed in their impact on eIF3 holo-complex formation and translation, they were each required for cancer cell proliferation and tumor growth. Remarkably, eIF3k showed the opposite pattern with depletion promoting global translation, cell proliferation, tumor growth, and stress resistance through repressing the synthesis of ribosomal proteins, especially RPS15A. Whereas ectopic expression of RPS15A mimicked the anabolic effects of eIF3k depletion, disruption of eIF3 binding to the

SUBMITTER: Prof. Dieter, A Wolf 

PROVIDER: S-SCDT-10_15252-EMBJ_2022112362 | biostudies-other |

REPOSITORIES: biostudies-other