A new paper has been published by Tomáš Bárta, Lucie Pešková and Aleš Hampl in Scientific Reports. The publication describes a new software tool for desing microRNA sponges, it also provides an experimental evidence of functionality of this tool.
MicroRNAs (miRNAs) are short non-coding RNA molecules that regulate the expression of their target genes at the post-transcriptional level by binding to their respective mRNAs. Upon hybridisation of the miRNA/messenger (m)RNA duplex, the target mRNA is cleaved and degraded or blocked from translation. The miRNAs represent key players in the regulation of multiple genes, and thus, virtually all cell processes, including cell cycle regulation, apoptosis, differentiation, and metabolism.
MiRNA sponges are exogenously introduced transcripts containing multiple tandem high-affinity binding sites to a miRNA of interest. These miRNA-binding molecules are competitive regulators that sequester specific miRNAs, thus preventing miRNA/mRNA interaction (see the figure below). MiRNA sponges are used in loss-of-function studies, where potent miRNA inhibition is desired. It should be noted that miRNA sponges may exhibit off-target effects by sequestering unspecific miRNAs. As the human genome contains thousands of miRNA sequences and given the small size of each mature miRNA (∼22 nucleotides), there is a high probability that poorly designed miRNA sponge constructs may exhibit unspecific sequestration of miRNAs. Therefore, sponge sequences must be carefully optimised to avoid the binding of other miRNAs.
In order to address this issue, the authors developed a web-based tool, microRNA sponge generator and tester (miRNAsong), which is freely available at: http://www.med.muni.cz/histology/miRNAsong. This tool allows the user to generate miRNA sponge sequences specific to a target miRNA, miRNA family and/or cluster.
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