DUSP3 modulates IRES‐dependent translation of mRNAs through dephosphorylation of the HNRNPC protein in cells under genotoxic stimulus

• DOI: 10.1111/boc.202300128
• Publication Date: 2024-03-28T03:19:40Z
• Authors: Pault Y. M. Ferruzo; Viktor K. Boell; Lilian C. Russo; Carla C. Oliveira; Fabio L. Forti
• Keywords: Polysome; Stress granule; Dephosphorylation

Abstract Background Information The dual‐specificity phosphatase 3 (DUSP3) regulates cell cycle progression, proliferation, senescence, and DNA repair pathways under genotoxic stress. This interacts with HNRNPC protein suggesting an involvement in the regulation of HNRNPC‐ribonucleoprotein complex stability. In this work, we investigate impact DUSP3 depletion on functions aiming to suggest new roles for enzyme. Results knockdown results tyrosine hyperphosphorylation state increasing its RNA binding ability. is present cytoplasm where it IRES trans‐acting factors (ITAF) complex, which recruits 40S ribosome mRNA during synthesis, thus facilitating translation mRNAs containing sequence response specific stimuli. accordance that, found that 40S, monosomes polysomes interacting HNRNPC, just like other previously identified substrates/interacting partners such as PABP NCL proteins. By downregulating DUSP3, Tyr‐phosphorylated preferentially binds IRES‐containing within ITAF complexes synchronized or stressed cells, evidenced by higher levels proteins c‐MYC XIAP, but not their measured qPCR. Under absence, increased phosphorylated‐HNRNPC/RNA interaction reduces HNRNPC‐p53 presence RNAs releasing p53 specialized cellular responses. Similarly, physically RNA‐dependent manner. Conclusions Significance Overall, can modulate responses stimuli at translational level maintaining stability HNRNPC‐ITAF regulating intensity specificity interactions RRM‐domain