Switching from repression to activation: microRNAs can up-regulate translation.
21 Dec 2007-Science (American Association for the Advancement of Science)-Vol. 318, Iss: 5858, pp 1931-1934
TL;DR: It is proposed that translation regulation by microRNPs oscillates between repression and activation during the cell cycle, and two well-studied microRNAs—Let-7 and the synthetic microRNA miRcxcr4—likewise induce translation up-regulation of target mRNAs on cell cycle arrest.
Abstract: AU-rich elements (AREs) and microRNA target sites are conserved sequences in messenger RNA (mRNA) 3' untranslated regions (3'UTRs) that control gene expression posttranscriptionally. Upon cell cycle arrest, the ARE in tumor necrosis factor-alpha (TNFalpha) mRNA is transformed into a translation activation signal, recruiting Argonaute (AGO) and fragile X mental retardation-related protein 1 (FXR1), factors associated with micro-ribonucleoproteins (microRNPs). We show that human microRNA miR369-3 directs association of these proteins with the AREs to activate translation. Furthermore, we document that two well-studied microRNAs-Let-7 and the synthetic microRNA miRcxcr4-likewise induce translation up-regulation of target mRNAs on cell cycle arrest, yet they repress translation in proliferating cells. Thus, activation is a common function of microRNPs on cell cycle arrest. We propose that translation regulation by microRNPs oscillates between repression and activation during the cell cycle.
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28 Jul 2005
TL;DR: PfPMP1）与感染红细胞、树突状组胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作�ly.
Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。
18,940 citations
TL;DR: The current understanding of miRNA target recognition in animals is outlined and the widespread impact of miRNAs on both the expression and evolution of protein-coding genes is discussed.
18,036 citations
Cites background from "Switching from repression to activa..."
...Indeed, under some circumstances, in particular those that induce cells to become quiescent, miRNA targeting of UTRs is reported to enhance rather than repress translation (Vasudevan et al., 2007, 2008)....
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TL;DR: This Review summarizes the current understanding of the mechanistic aspects of microRNA-induced repression of translation and discusses some of the controversies regarding different modes of micro RNA function.
Abstract: MicroRNAs constitute a large family of small, approximately 21-nucleotide-long, non-coding RNAs that have emerged as key post-transcriptional regulators of gene expression in metazoans and plants. In mammals, microRNAs are predicted to control the activity of approximately 30% of all protein-coding genes, and have been shown to participate in the regulation of almost every cellular process investigated so far. By base pairing to mRNAs, microRNAs mediate translational repression or mRNA degradation. This Review summarizes the current understanding of the mechanistic aspects of microRNA-induced repression of translation and discusses some of the controversies regarding different modes of microRNA function.
4,973 citations
TL;DR: This work has revealed unexpected diversity in their biogenesis pathways and the regulatory mechanisms that they access, which has direct implications for fundamental biology as well as disease etiology and treatment.
4,490 citations
Cites background from "Switching from repression to activa..."
...Lymphocyte growth arrest induces TNFa expression that is required for macrophage maturation; miR-369-3p switches from a repressor to an activator of TNFa translation when cells in culture are growth arrested (Vasudevan et al., 2007)....
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...The miRNA let-7 and an artificial miRNA (CXCR4) repress translation in proliferating human cells but change into translational activators when the cell cycle is arrested at the G1 checkpoint by serum starvation (Vasudevan et al., 2007)....
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...N IH -PA Author M anuscript N IH -PA Author M anuscript N IH -PA Author M anuscript repressor to an activator of TNFα translation when cells in culture are growth arrested (Vasudevan et al., 2007)....
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TL;DR: This work has shown that the regulation of miRNA metabolism and function by a range of mechanisms involving numerous protein–protein and protein–RNA interactions has an important role in the context-specific functions of miRNAs.
Abstract: MicroRNAs (miRNAs) are a large family of post-transcriptional regulators of gene expression that are ~21 nucleotides in length and control many developmental and cellular processes in eukaryotic organisms. Research during the past decade has identified major factors participating in miRNA biogenesis and has established basic principles of miRNA function. More recently, it has become apparent that miRNA regulators themselves are subject to sophisticated control. Many reports over the past few years have reported the regulation of miRNA metabolism and function by a range of mechanisms involving numerous protein-protein and protein-RNA interactions. Such regulation has an important role in the context-specific functions of miRNAs.
4,123 citations
References
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28 Jul 2005
TL;DR: PfPMP1）与感染红细胞、树突状组胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作�ly.
Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。
18,940 citations
TL;DR: Possible mechanisms by which miRNAs control translation and mRNA degradation are discussed, an emerging theme is that mi RNAs, and siRNAs to some extent, target m RNAs to the general eukaryotic machinery for mRNA degradation and translation control.
Abstract: The control of translation and mRNA degradation is an important part of the regulation of gene expression. It is now clear that small RNA molecules are common and effective modulators of gene expression in many eukaryotic cells. These small RNAs that control gene expression can be either endogenous or exogenous micro RNAs (miRNAs) and short interfering RNAs (siRNAs) and can affect mRNA degradation and translation, as well as chromatin structure, thereby having impacts on transcription rates. In this review, we discuss possible mechanisms by which miRNAs control translation and mRNA degradation. An emerging theme is that miRNAs, and siRNAs to some extent, target mRNAs to the general eukaryotic machinery for mRNA degradation and translation control.
2,030 citations
TL;DR: Observations suggest that Adenylate/uridylate-rich elements play a critical role in the regulation of gene expression during cell growth and differentiation and in the immune response.
1,955 citations
TL;DR: The ability of an miRNA to translationally repress a target mRNA is largely dictated by the free energy of binding of the first eight nucleotides in the 5' region of the miRNA, however, G:U wobble base-pairing in this region interferes with activity beyond that predicted on the basis of thermodynamic stability.
Abstract: MicroRNAs (miRNAs) are a class of noncoding RNAs found in organisms as evolutionarily distant as plants and mammals, yet most of the mRNAs they regulate are unknown. Here we show that the ability of an miRNA to translationally repress a target mRNA is largely dictated by the free energy of binding of the first eight nucleotides in the 5' region of the miRNA. However, G:U wobble base-pairing in this region interferes with activity beyond that predicted on the basis of thermodynamic stability. Furthermore, an mRNA can be simultaneously repressed by more than one miRNA species. The level of repression achieved is dependent on both the amount of mRNA and the amount of available miRNA complexes. Thus, predicted miRNA:mRNA interactions must be viewed in the context of other potential interactions and cellular conditions.
1,744 citations
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TL;DR: In this article, the existence of a monotone interpolating function with the same index set was shown to be necessary and sufficient for continuous interpolating functional if the index set I is finite, but not sufficient if I is infinite.
Abstract: AbMnwt. Let P = (pi 1 i E I} and 8 = {qi 1 i E I} be sets of partis! functions with the same index set Z. We say that Cp is an interpolating function (from P to 0) if @(pi) = qi for each i. We give simple necessary and sufficient conditions for the existence of a monotone interpolating functional. Wti show that these same conditions are necessary and sufficient for the existence of a continuous interpolating functional if the index set I is finite, but that they are not sufficient if the index set is infinite.
1,584 citations