title: 7SL RNA represses p53 translation by competing with HuR.
abstract: Noncoding RNAs (ncRNAs) and RNA-binding proteins are potent post-transcriptional regulators of gene expression. The ncRNA 7SL is upregulated in cancer cells, but its impact upon the phenotype of cancer cells is unknown. Here, we present evidence that 7SL forms a partial hybrid with the 3'-untranslated region (UTR) of TP53 mRNA, which encodes the tumor suppressor p53. 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. Silencing 7SL led to increased binding of HuR to TP53 mRNA, an interaction that led to the promotion of p53 translation and increased p53 abundance. 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.
authors.affiliation: Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA abdelmohsenk@mail.nih.gov.
authors.forename: Kotb
authors.initials: K
authors.lastname: Abdelmohsen
authors.affiliation: Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
authors.forename: Amaresh C
authors.initials: AC
authors.lastname: Panda
authors.affiliation: Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
authors.forename: Min-Ju
authors.initials: MJ
authors.lastname: Kang
authors.affiliation: Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
authors.forename: Rong
authors.initials: R
authors.lastname: Guo
authors.affiliation: Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
authors.forename: Jiyoung
authors.initials: J
authors.lastname: Kim
authors.affiliation: Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Grammatikakis
authors.affiliation: Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
authors.forename: Je-Hyun
authors.initials: JH
authors.lastname: Yoon
authors.affiliation: Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
authors.forename: Dawood B
authors.initials: DB
authors.lastname: Dudekula
authors.affiliation: Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
authors.forename: Ji Heon
authors.initials: JH
authors.lastname: Noh
authors.affiliation: Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Yang
authors.affiliation: Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Martindale
authors.affiliation: Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA abdelmohsenk@mail.nih.gov.
authors.forename: Myriam
authors.initials: M
authors.lastname: Gorospe
mesh_terms: D020413:3' Untranslated Regions; D001343:Autophagy; D001667:Binding, Competitive; D059447:Cell Cycle Checkpoints; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D016922:Cellular Senescence; D051959:ELAV Proteins / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D006801:Humans; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D020733:RNA, Small Cytoplasmic / Q000378:metabolism*; D018271:Signal Recognition Particle / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; C115990:7SL RNA; D051959:ELAV Proteins; D012333:RNA, Messenger; D020733:RNA, Small Cytoplasmic; D018271:Signal Recognition Particle; D016159:Tumor Suppressor Protein p53