Constantly edited genetic material
The fidelity of genomic content is compromised by two mechanisms namely genome editing and active retrotransposons. Even within a single cell, these processes can generate a large number of different transcripts. The EU-funded GENEDISCREEN (Identification and screen of RNA editing in the human genome) project set out to study and provide insight into these poorly understood molecular phenomena. For this purpose, project scientists have carefully studied the human genome and compared RNA sequences to their source DNA to discover millions of previously undetected editing sites. The number of mammalian conserved editing sites was found to be very small, with unique features and distribution compared to the non-conserved sites. These observations led scientists to speculate that the conserved sites must play a role in mammalian biology and that editing could be also implicated in various diseases. Further work was performed to delineate if genome editing contributes to retrotransposon maintenance throughout evolution. Retrotransposons are genetic elements capable of jumping from one genome site to another site and constitute ubiquitous components of the DNA of many eukaryotic organisms. Study results demonstrated that editing enables the genome to utilise these transformed sequences for its benefit and essentially attenuates retrotransposon mutagenicity. This antiviral mechanism most likely accelerates evolution of both retrotransposons and their hosts. In another part of the project, scientists discovered significantly higher levels of RNA editing in cancer samples compared to normal tissues. This finding suggested that editing may synergise with genomic DNA alterations in driving carcinogenesis. Therefore, editing events may serve as novel candidates for therapeutic and diagnostic purposes. Collectively the results of the GENEDISCREEN study provide an unprecedented level of understanding on RNA and DNA editing mechanisms. The finding about constant genome editing occurring at both the DNA and RNA level at millions of sites disclosed an unparalleled level of genomic diversity within the same cell or organism.
