7SL RNA represses p53 translation by competing with HuR.
Bottom Line: The interaction of 7SL with TP53 mRNA reduced p53 translation, as determined by analyzing p53 expression levels, nascent p53 translation and TP53 mRNA association with polysomes.We propose that the competition between 7SL and HuR for binding to TP53 3'UTR contributes to determining the magnitude of p53 translation, in turn affecting p53 levels and the growth-suppressive function of p53.Our findings suggest that targeting 7SL may be effective in the treatment of cancers with reduced p53 levels.
Affiliation: Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA email@example.com.Show MeSH
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Mentions: Several studies underscore the role of HuR in orchestrating anti-apoptotic and pro-survival programs (13,27). In agreement with this influence, HuR silencing decreased cell numbers and silencing both HuR and 7SL decreased cell numbers even further (Supplementary Figure S4A). Therefore, we sought to study in more detail the cellular response to lowering 7SL levels. The 7SL silencing-triggered decrease in cell numbers was specifically dependent on p53, since p53-deficient (p53KO) HCT116 cells were refractory to the loss in cell number after silencing 7SL (Supplementary Figure S4B and C). These data indicated that silencing 7SL caused growth arrest at least in part by inducing p53 levels. Thus, we investigated other p53-regulated cellular processes—cell cycle, senescence and autophagy. By fluorescence-activated cell sorting (FACS) analysis, silencing 7SL led to an increase in the G1 and G2 compartments and a decrease in S-phase cells (Figure 6A). 7SL silencing also lowered [3H]-thymidine incorporation (Figure 6B), further indicating that silencing 7SL inhibited DNA replication, which occurs during S phase; conversely, overexpressing 7SL as explained in Figure 2E increased [3H]-thymidine incorporation (Supplementary Figure S4E).
Affiliation: Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA firstname.lastname@example.org.