Genetics. Small RNAs reveal an activating side.

Science (Impact Factor: 31.48). 12/2006; 314(5800):741-2. DOI: 10.1126/science.314.5800.741a
Source: PubMed
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    ABSTRACT: RNA activation (RNAa) is a novel mechanism in which short RNA duplexes, referred to as small activating RNAs (saRNAs), enable sequence-specific gene activation capable of lasting up to 2 weeks. RNAa was named in contrast to RNA interference (RNAi). Although many mysteries remain, increasing evidence demonstrates that RNAa not only provides a novel mechanism for the study of gene function and regulation, but also holds exciting potential for clinical translation to therapeutic modality against cancers. In this review, we will focus on the potential applications of RNAa in cancer studies and therapeutics.
    Cancer Letters 09/2014; 355(1). DOI:10.1016/j.canlet.2014.09.004 · 5.02 Impact Factor
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    ABSTRACT: Background MicroRNA (miRNA) directed gene repression is an important mechanism of posttranscriptional regulation. Comprehensive analyses of how microRNA influence biological processes requires paired miRNA-mRNA expression datasets. However, a review of both GEO and ArrayExpress repositories revealed few such datasets, which was in stark contrast to the large number of messenger RNA (mRNA) only datasets. It is of interest that numerous primary miRNAs (precursors of microRNA) are known to be co-expressed with coding genes (host genes). Results We developed a miRNA-mRNA interaction analyses pipeline. The proposed solution is based on two miRNA expression prediction methods – a scaling function and a linear model. Additionally, miRNA-mRNA anti-correlation analyses are used to determine the most probable miRNA gene targets (i.e. the differentially expressed genes under the influence of up- or down-regulated microRNA). Both the consistency and accuracy of the prediction method is ensured by the application of stringent statistical methods. Finally, the predicted targets are subjected to functional enrichment analyses including GO, KEGG and DO, to better understand the predicted interactions. Conclusions The MMpred pipeline requires only mRNA expression data as input and is independent of third party miRNA target prediction methods. The method passed extensive numerical validation based on the binding energy between the mature miRNA and 3’ UTR region of the target gene. We report that MMpred is capable of generating results similar to that obtained using paired datasets. For the reported test cases we generated consistent output and predicted biological relationships that will help formulate further testable hypotheses.
    BMC Genomics 11/2012; 13(1):620. DOI:10.1186/1471-2164-13-620 · 4.04 Impact Factor
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    ABSTRACT: Abstract Small RNA programmed Argonautes are sophisticated cellular effector platforms known to be involved in a diverse array of functions ranging from mRNA cleavage, translational inhibition, DNA elimination, epigenetic silencing, alternative splicing and even gene activation. First observed in human cells, small RNA-induced gene activation, also known as RNAa, involves the targeted recruitment of Argonaute proteins to specific promoter sequences followed by induction of stable epigenetic changes which promote transcription. The existence of RNAa remains contentious due to its elusive mechanism. A string of recent studies in C. elegans provides unequivocal evidence for RNAa's fundamental role in sculpting the epigenetic landscape and maintaining active transcription of endogenous genes and supports the presence of a functionally sophisticated network of small RNA-Argonaute pathways consisting of opposite yet complementary "yin and yang" regulatory elements. In this review, we summarize key findings from recent studies of endogenous RNAa in C. elegans, with an emphasis on the Argonaute protein CSR-1.
    RNA Biology 01/2015; 11(10). DOI:10.4161/15476286.2014.972853 · 5.38 Impact Factor