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: Since 7SL is the RNA component of the signal recognition particle (SRP), we studied if the reduction in p53 protein levels was affected by other SRP components. Silencing protein components of the SRP (SRP19, SRP54 or SRP68; Figure 3A) lowered p53 abundance (Figure 3B) but did not affect the levels of TP53 mRNA (Figure 3B) or 7SL (Figure 3C). In addition, silencing SRP proteins did not significantly affect cell viability by 48 h after silencing SRP proteins (Figure 3D). These findings suggest that silencing SRP proteins does not recapitulate the increase in p53 elicited by silencing 7SL in HeLa cells. To test this possibility further, glycerol gradients were studied in order to study if 7SL is present in fractions devoid of SRP proteins. As shown in Figure 3E–G, SRP54 and SRP68 overlapped substantially with 7SL (particularly in fractions 5 through 9 of the gradient), but a sizeable amount of 7SL was found outside of these fractions. In fact, >30% of 7SL was detected in fractions that did not have SRP54 or SRP68. These results support the notion that a subset of 7SL exists outside of the SRPs and further indicate that the influence of 7SL on p53 expression is likely independent of its function as part of the SRP.
Affiliation: Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA firstname.lastname@example.org.