Exploring the dark matter of the human genome

Using a oligonucleotide-based molecules to probe and elucidate the biological role of ncRNAs

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The sequencing of the human genome substantially revolutionized the concept of gene. Genome-wide association studies further broadened our knowledge on the organization and crosstalk between genes . Only a small percentage of our genome (about 2-3%) codes for proteins, while the remaining 97-98% , the so-called “dark matter” of the genome, is represented by non-coding RNAs (ncRNAs). Littlee information is available on the role of long non coding RNAs (lncRNAs) and, to complicate the situation, more and more lncRNA sequences are discovered every day. Some lncRNA sequences are reported to host the transcripts of small ncRNAs, some are known to control the expression of genes located on the same chromosome, while other regulate the expression of genes located at independent loci. Increasingly, experimental evidences support the hypothesis that a number of non-coding RNAs are involved in the organization and regulation of human genes. It has been proposed that genomic variants associated with diseases affect regulatory properties of non-coding RNAs in mammalian cells. The network of interactions between coding and non-coding genes seems quite puzzling.

Interestingly, if we analyze the experimental techniques employed to illuminate the function of ncRNAs, we will notice that many of the tools employed to this end (for example those aimed at identifying the ncRNA interactors or those aimed at determining the subcellular localization of ncRNAs) rely on oligonucleotides or oligonucleotide analogues. This observation suggests how important is a deep understanding of the binding/stability/ conformational properties of oligonucleotides and how this will help us to develop new tools to control cellular processes regulated by non coding RNA sequences.

Read more in: “Exploring the dark matter of the human genome using oligonucleotide-based molecules” Avitabile C. et al. Future Medicinal Chemistry, 2015, 7 (13) , 1627-1630.

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Alessandra Romanelli

PhD, University of Naples "Federico II"

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