By Patrick Arbuthnot, Marc S Weinberg
Because the discovery of RNA interference (RNAi) in 1998, examine at the subject has complicated at a magnificent speed. Small RNAs and, specifically, micro RNAs (miRNAs) play a basic position in gene law throughout the activation of RNAi. distinctive insights into the mechanisms of RNAi have ended in a more robust figuring out of gene law in basic and affliction states, and thereby enabled the exploitation of RNAi for various purposes. during this booklet, a global panel of RNAi specialists significantly reports the main fascinating advances in simple utilized RNAi study, highlighting the functions in RNAi-based treatments and discussing the technical hurdles that stay. themes protecting the elemental organic points of utilized RNAi examine comprise: the position of miRNAs in trinucleotide repeat problems * miRNAs and HIV pathogenesis * miRNAs for epigenetic gene silencing * the function of miRNAs in virus-related cancers * non-canonical miRNA biogenesis. within the region of RNAi-based treatment, subject matters contain: harnessing RNAi for the therapy of viral infections * optimizing the layout of exogenous RNAi activators * blocking off miRNA functionality with man made brokers * somatic phone reprogramming * high-content miRNA-based screening instruments * using miRNA aim websites for keep an eye on of transgene expression. The booklet may be crucial interpreting for everybody considering RNAi examine, drug discovery and supply, biomedical engineering, and biomaterials. [Subject: Molecular Biology, Genomics, existence technology]
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Extra info for Applied RNAi: From Fundamental Research to Therapeutic Applications
2009). , 2010). Using luciferase reporter constructs Lytle et al. (2007) showed that miRNAs can repress transcripts with 5′ UTR or 3′ UTR targets equally in human cells. Morreti et al. (2010) used an immunoprecipitation protocol to pulldown mRNAs that differentially associate with AGO2 after transfection with mimics of either miR-1 or miR-124. , 2008). Similarly, Grey at al. , 2010). Interestingly, Lee and co-workers showed that some miRNAs can simultaneously target both untranslated regions.
E. , 2005). , 2010). , 2008). , 2012). , 2008). Vasudevan and co-workers showed that differential miRNA-mediated silencing and activation is context dependent. In the case of tumour necrosis factor–alpha (TNF-α), an AU-rich element (ARE) found in the 3′ UTR becomes a translational activation motif following cell cycle arrest. Association of activating factors with the TNFα mRNA was directed by miR-369-3. , 2007). An exogenous small RNA was also able to switch between silencing and activation depending on whether the cells were grown in the presence or absence of serum respectively, thereby demonstrating the generality of this phenomenon.
Perhaps the most well understood example of miRNA-mediated translational activation (on account of its pharmacological significance) is in the case of the hepatitis C virus (HCV) RNA. e. , 2005). , 2010). , 2008). , 2012). , 2008). Vasudevan and co-workers showed that differential miRNA-mediated silencing and activation is context dependent. In the case of tumour necrosis factor–alpha (TNF-α), an AU-rich element (ARE) found in the 3′ UTR becomes a translational activation motif following cell cycle arrest.
Applied RNAi: From Fundamental Research to Therapeutic Applications by Patrick Arbuthnot, Marc S Weinberg