NAR Breakthrough Article 7SL RNA represses p53 translation by competing with HuR

被引：123

作者：

Abdelmohsen, Kotb ^{[1
]}

Panda, Amaresh C. ^{[1
]}

Kang, Min-Ju ^{[1
]}

Guo, Rong ^{[1
]}

Kim, Jiyoung ^{[1
]}

Grammatikakis, Ioannis ^{[1
]}

Yoon, Je-Hyun ^{[1
]}

Dudekula, Dawood B. ^{[1
]}

Noh, Ji Heon ^{[1
]}

Yang, Xiaoling ^{[1
]}

Martindale, Jennifer L. ^{[1
]}

Gorospe, Myriam ^{[1
]}

机构：

[1] NIA, Genet Lab, NIH, Baltimore, MD 21224 USA

来源：

NUCLEIC ACIDS RESEARCH | 2014年 / 42卷 / 15期

基金：

美国国家卫生研究院;

关键词：

BINDING PROTEIN HUR; LONG NONCODING RNA; POSTTRANSCRIPTIONAL GENE-REGULATION; TARGET MESSENGER-RNAS; TUMOR SUPPRESSION; DNA-DAMAGE; EXPRESSION; PHOSPHORYLATION; GROWTH; CANCER;

D O I：

10.1093/nar/gku686

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

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.

引用

页码：10099 / 10111

页数：13

共 42 条

[1]

Posttranscriptional orchestration of an anti-apoptotic program by HuR [J].