LincRNA-p21 Suppresses Target mRNA Translation

被引:1360
作者
Yoon, Je-Hyun [1 ]
Abdelmohsen, Kotb [1 ]
Srikantan, Subramanya [1 ]
Yang, Xiaoling [1 ]
Martindale, Jennifer L. [1 ]
De, Supriyo [2 ]
Huarte, Maite [3 ]
Zhan, Ming [4 ]
Becker, Kevin G. [2 ]
Gorospe, Myriam [1 ]
机构
[1] NIA, Lab Mol Biol & Immunol, Intramural Res Program, NIH, Baltimore, MD 21224 USA
[2] NIA, Res Resources Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA
[3] Univ Navarra, CIMA, Dept Oncol, Pamplona 31008, Spain
[4] Methodist Hosp, Dept Syst Med & Bioengn, Res Inst, Houston, TX 77030 USA
关键词
BINDING PROTEIN HUR; LONG NONCODING RNAS; EXPRESSION; REPRESSION; DISEASE;
D O I
10.1016/j.molcel.2012.06.027
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
Mammalian long intergenic noncoding RNAs (lincRNAs) are best known for modulating transcription. Here we report a posttranscriptional function for lincRNA-p21 as a modulator of translation. Association of the RNA-binding protein HuR with lincRNA-p21 favored the recruitment of let-7/Ago2 to lincRNA-p21, leading to lower lincRNA-p21 stability. Under reduced HuR levels, lincRNA-p21 accumulated in human cervical carcinoma He La cells, increasing its association with JUNB and CTNNB1 mRNAs and selectively lowering their translation. With elevated HuR, lincRNA-p21 levels declined, which in turn derepressed JunB and beta-catenin translation and increased the levels of these proteins. We propose that HuR controls translation of a subset of target mRNAs by influencing lincRNA-p21 levels. Our findings uncover a role for lincRNA as a posttranscriptional inhibitor of translation.
引用
收藏
页码:648 / 655
页数:8
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