Basic principles of noncoding RNAs in epigenetics

The majority of our genome is pervasively transcribed, but not translated into proteins. These highly heterogeneous noncoding transcripts proved to have key cellular functions. One of the major features described for noncoding RNAs is their ability to create tridimensional structures that serve as scaffold, guide, or decoy for proteins and other transcripts. Recent data support the notion of a prominent role of these interactions in the epigenetic modulation of gene expression mediated by chromatin remodelers and histone modifiers that act converging environmental signals to DNA. These epigenetic marks have the peculiarity to be maintained throughout generations, even when the cue is no longer present without altering DNA sequence. Given the key importance of noncoding RNAs (ncRNAs) in cell physiology, therapeutic approaches based on ncRNAs targeting via diverse tools are now under development and offer many advantages over classical protein-targeting therapies. Understanding the basis of ncRNAs' interaction with the epigenetic machinery is therefore of key interest in order to expand our knowledge on the molecular mechanisms driving epigenetic modifications and to guide the development of novel and more specific therapeutic approaches. Noncoding transcripts not only act within the cell in which they are transcribed but also can be actively or passively released to body fluids where pathological alterations in the expression of noncoding genes can be detected. These pathology-related signatures can be easily exploited as biomarkers for disease onset and progression.