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: The RBP HuR binds the 3′UTR of TP53 mRNA and promotes its translation following irradiation with ultraviolet light (23). Recent HuR PAR-CLIP data revealed that the sites where HuR binds within TP53 3′UTR (11) were adjacent to the site of interaction with 7SL (Figure 4A; yellow, HuR interaction sites; green, putative 7SL sites). Since HuR enhances p53 abundance, 7SL lowers it, and both HuR and 7SL bind TP53 3′UTR, we hypothesized that HuR and 7SL specifically compete for binding to TP53 mRNA. To test this possibility, we first silenced 7SL and studied if this intervention affected HuR binding to target mRNAs (15,18,23). As shown, silencing 7SL selectively enhanced HuR binding to TP53 mRNA, but not to VHL, SIRT1 or NCL mRNAs (Figure 4B).
Affiliation: Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA firstname.lastname@example.org.