Abstract

Small double-strand RNA (dsRNA) molecules can activate endogenous genes via an RNA-based promoter targeting mechanism. RNA activation (RNAa) is an evolutionarily conserved mechanism present in diverse eukaryotic organisms ranging from nematodes to humans. Small activating RNAs (saRNAs) involved in RNAa have been successfully used to activate gene expression in cultured cells, and thereby this emergent technique might allow us to develop various biotechnological applications, without the need to synthesize hazardous construct systems harboring exogenous DNA sequences. Accordingly, this thematic issue aims to provide insights into how RNAa cellular machinery can be harnessed to activate gene expression leading to a more effective clinical treatment of various diseases.

Highlights

  • Small interfering RNAs and microRNAs, key regulators of gene expression, are recognized as small double-stranded RNA molecules [1,2,3]

  • The first reports showed that gene expression can be activated by synthetic double-stranded RNA (dsRNA) targeting promoter regions, more recent studies confirmed that RNA activation” (RNAa) is an evolutionarily conserved mechanism present in diverse eukaryotic organisms ranging from nematodes to humans [14,15]

  • Apart from promoter sequences, which are known as the main target sites for small activating RNAs (saRNAs), gene activation by small RNA fragments could operate in any genomic region where antisense transcripts are presented

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Summary

Introduction

Small interfering RNAs (siRNAs) and microRNAs (miRNAs), key regulators of gene expression, are recognized as small double-stranded RNA (dsRNA) molecules [1,2,3]. Cell-mediated brain repair suffers from poor survival rate of transplanted cells and the low efficiency of differentiation into neuronal cells [23] Diodato and his colleagues have used pre-miRNAs (as activating RNAs) to increase the expression of Emx, a human homeobox transcription factor modulating a number of developmental mechanisms such as development of cerebral cortex. In all reported studies, targeting of promoter regions by small dsRNA or small hairpin RNA (shRNA) leads to transcriptional activation of cardiovascular genes, which could open the way for therapeutic strategies. Similar to siRNA knockdown, antisense transcript distraction following the sense oligoribonucleotide electroporation could represent a secondary phenomenon of the activation of the RNAi machinery This activation may result in a change in epigenetic modifications at the locus, leading to the induction of Cdk transcription as described for several genes [1,53]. Injection into wild-type blastocysts of RNA-programmed ES cells contributes to heart development in vivo, indicating that a transient RNA activation system is sufficient to create a cardiac differentiation “memory” in cells and may represent a novel tool for RNA–cell reprogramming applied in regenerative medicine

Small Activating RNAs
Conclusions and Future Perspectives
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