Our understanding of the functional output of the mammalian genome has enormously increased in the last two decades, and it is fair to say that this has profoundly changed our comprehension of how a cell works and of how evolution has shaped biological complexity.

Our initiative focuses on non-coding RNAs whose knowledge has experienced the most rapid growth in the recent years, thanks to the advent of omic technologies and next-generation sequencing. For years we have believed that the functions of genomes dwell only in the genes that encode proteins, called protein-coding genes. These genes produce messenger RNAs which are converted into proteins, structural macromolecules or enzymes that function as building blocks or by catalyzing chemical reactions within the cell.

Differently from messenger RNAs, non-coding RNAs are not associated with protein products, nevertheless they can still perform highly specialized functions in the cell. A better understating of the non-coding RNA functions is therefore pivotal to uncover the mechanisms underlying diseases such as Neurodevelopmental, Neurodegenerative and Cancer.

Due to their complexity and the difficulties in understanding their mechanisms, non-coding RNAs are a demanding challenge for scientists. However, these molecules represent one of the most promising resources to be exploited for biotechnology and human health.

One of the most unexpected surprises of the Human Genome Project was the discovery that the number of protein-coding genes found in our genome was significantly smaller than expected.
The scientific community was thus faced with a true enigma: how is it possible to explain the incredible level of complexity and phenotypic diversity of human being starting from such a modest set of genes? The discovery of the world of non-coding RNAs revealed the answer…
Thanks to new omic technologies such as microarrays and next-generation sequencing (NGS), scientists have discovered that the human genome bears many thousands of non-coding RNAs. Biology is slowly understanding that it is precisely these molecules that have allowed the development of complexity and the diversification of gene regulation that has allowed the evolution of species.

The term non-coding RNA is very general and includes several classes of RNA molecules, which have in common the ability to perform a regulatory function without generating of a protein product. Classes of interest include long non-coding RNAs (lncRNAs), small non-coding RNAs (sncRNAs) and transcripts derived from Transposable Elements (TEs), such as SINE (short interspersed nuclear element) and LINE (long interspersed nuclear element). Among sncRNAs, several classes have been identified including enhancer RNA (eRNAs), microRNAs (miRNA), PIWI-interacting RNAs (piwiRNAs) and circular RNA (circRNAs).

lncRNAs are exemplary of the versatility of these systems. They are flexible modular scaffolds that combine a structure with independent domains that bind protein complexes, with the recognition and modulation of RNA/DNA targets. 
These classes of non-coding RNAs present virtually limitless opportunities to spatio-temporally modify gene expression; RNA-based drugs can thus extend the druggable genome with high specificity to both protein-coding genes and regulatory regions, and therefore provide an almost unlimited reservoir of new pharmacological agents. Further, they are the quintessential personalized medicine, since they can be tailored to the genomic repertory of a single patient: this is critical for a step change of therapeutic intervention, moving from a one-size-fits-all approach to personalised medicine.