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: Long ncRNAs can enhance or suppress gene expression by interacting directly with mRNAs (2). A BLAST survey to identify possible interactions between 7SL and regulators of cell growth revealed that 7SL was predicted to form extensive regions of sense–antisense interaction with the 3′UTR of the TP53 mRNA (nucleotides 2209–2367; Figure 2A, Supplementary Figure S2); sequence identities were 85–93%. Other putative interaction partners of 7SL are listed (Supplementary Table S1). To verify if endogenous 7SL and TP53 mRNAs formed hybrid RNA interactions, we designed biotinylated AS oligomers complementary to TP53 mRNA (TP53-biot-ASO), to a negative control (the lncRNA MIAT, MIAT-biot-ASO), and to mRNAs encoding insulin (INS-biot-ASO) and Sirtuin-1 (SIRT1-biot-ASO). Incubation of lysates prepared from HeLa cells with biot-ASOs revealed that 7SL was enriched in TP53-biot-ASO pulldown samples, but not in the other biot-ASO pulldowns, indicating that 7SL selectively associated with TP53 mRNA (Figure 2B). The enrichment of GAPDH mRNA in the pulldown samples was measured to assess background RNA binding to biot-ASOs.
Affiliation: Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA firstname.lastname@example.org.