Analysis of turnover and translation regulatory RNA-Binding protein expression through binding to cognate mRNAs

被引:179
作者
Pullmann, Rudolf, Jr. [1 ]
Kim, Hyeon Ho [1 ]
Abdelmohsen, Kotb [1 ]
Lal, Ashish [1 ]
Martindale, Jennifer L. [1 ]
Yang, Xiaoling [1 ]
Gorospe, Myriam [1 ]
机构
[1] NIA, Cellular & Mol Biol Lab, Intramural Res Program, NIH, Baltimore, MD 21228 USA
关键词
D O I
10.1128/MCB.00500-07
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
RNA-binding proteins (RBPs) that associate with specific mRNA sequences and function as mRNA turnover and translation regulatory (TTR) RBPs are emerging as pivotal posttranscriptional regulators of gene expression. However, little is known about the mechanisms that govern the expression of TTR-RBPs. Here, we employed human cervical carcinoma HeLa cells to test the hypothesis that TTR-RBP expression is influenced posttranscriptionally by TTR-RBPs themselves. Systematic testing of the TTR-RBPs AUF1, HuR, KSRP, NF90, TIA-1, and TIAR led to three key discoveries. First, each TTR-RBP was found to associate with its cognate mRNA and with several other TTR-RBP-encoding mRNAs, as determined by testing both endogenous and biotinylated transcripts. Second, silencing of individual TTR-RBPs influenced the expression of other TTR-RBPs at the mRNA and/or protein level. Third, further analysis of two specific ribonucleoprotein (RNP) complexes revealed that TIA-1 expression was controlled via HuR-enhanced mRNA stabilization and TIAR-repressed translation. Together, our findings underscore the notion that TTR-RBP expression is controlled, at least in part, at the posttranscriptional level through a complex circuitry of self- and cross-regulatory RNP interactions.
引用
收藏
页码:6265 / 6278
页数:14
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