MicroRNA-offset RNAs (moRNAs): by-product spectators or functional players?

microRNA offset RNAs (moRNAs) were recently discovered by massive sequencing of short RNAs in a simple chordate and then found in normal human cells and solid tumours. Also, viral moRNAs are expressed in herpesviruses-infected human cells. moRNAs biogenesis is related to miRNA precursors processing, but molecular mechanisms are still unclear. moRNAs are conserved across species, prevalently produced by the 5' arm of the precursor, and nuclear-enriched, so they may be a new class of regulators, whose qualitative alteration and/or expression disregulation might impact on human diseases. Thus, there is an impelling need for functional characterization of moRNAs, and of other non-coding RNAs increasingly discovered by deep sequencing data analysis, in order to acquire biological knowledge possibly useful for translational medicine.