Kedde Martijn, Agami Reuven
The Netherlands Cancer Institute, Division of Tumor Biology, Amsterdam, The Netherlands.
Cell Cycle. 2008 Apr 1;7(7):899-903. doi: 10.4161/cc.7.7.5644. Epub 2008 Jan 24.
MicroRNAs (miRNAs) are genes involved in normal development and cancer. They inhibit gene expression by associating with 3'-Untranslated regions (3'UTRs) of messenger RNAs (mRNAs), and are thought to regulate a large proportion of protein coding genes. However, it is becoming apparent that miRNA activity is not necessarily always determined by its expression in the cell. MiRNA activity can be affected by RNA-binding proteins (RBPs). For example, the RNA-binding protein HuR associates with the 3'UTR of the CAT1 mRNA after stress, counteracting the effect of miR-122. Second, we found that the expression of an RNA-binding protein called Dead end (Dnd1) prohibits the function of several miRNAs by blocking the accessibility of target mRNAs.(2) Dnd1 function is essential for proper development of primordial germ cells (PGCs) in zebrafish and mammals, indicating a crucial role for RBP/miRNA interplay on 3'UTRs of mRNAs in developmental decisions. In this perspective we discuss the interplay between RBPs and miRNAs in the context of germ cells and review current observations implicating RBPs in miRNA function.
微小RNA(miRNA)是参与正常发育和癌症的基因。它们通过与信使核糖核酸(mRNA)的3'-非翻译区(3'UTR)结合来抑制基因表达,并且被认为可调控很大一部分蛋白质编码基因。然而,越来越明显的是,miRNA的活性不一定总是由其在细胞中的表达所决定。miRNA活性会受到RNA结合蛋白(RBP)的影响。例如,应激后RNA结合蛋白HuR会与CAT1 mRNA的3'UTR结合,抵消miR-122的作用。其次,我们发现一种名为Dead end(Dnd1)的RNA结合蛋白的表达会通过阻断靶mRNA的可及性来抑制几种miRNA的功能。(2)Dnd1的功能对于斑马鱼和哺乳动物中原始生殖细胞(PGC)的正常发育至关重要,这表明RBP/miRNA在mRNA的3'UTR上的相互作用在发育决策中起着关键作用。在此观点中,我们讨论了生殖细胞背景下RBP与miRNA之间的相互作用,并综述了目前有关RBP参与miRNA功能的观察结果。