Apart from the general presumption that most ncRNAs will be involved in regulation, variations in which will often have, individually, subtle effects on phenotype, there is, in fact, general evidence of their positive genetic signatures, as ncRNAs underpin most, if not all, complex genetic processes in the higher organisms. These include RNA interference-related phenomena such as co-suppression and transcriptional gene silencing [132], [173]–[176], as well as position effect variegation [177],[178], hybrid dysgenesis [179], parental imprinting, X-chromosome dosage compensation and allelic exclusion [180], germ cell reprogramming [181], and paramutation [182],[183], all of which involve epigenetic processes. Indeed, as noted already, there is increasing evidence that a major function of ncRNAs, both small and large, is the regulation of epigenetic memory through modifications to DNA and chromatin structure, involving the recruitment of DNA methyltransferases, histone-modifying enzymes, and chromatin remodelling complexes to their appropriate sites of action (including ncRNA genes themselves) in particular cells at particular stages of differentiation (for reviews, see [12],[89],[184]; also Table 1).
