RNA editing - Common, Hidden Mutations
Erez Levanon is an associate professor at the faculty of life sciences of Bar-Ilan University in Israel. He received his PhD from Tel-Aviv University after graduating the Adi Lautman Interdisciplinary Program for Outstanding Students and was a postdoctoral research follow at the genetics department of Harvard Medical School. Prior to that, he was a senior scientist in Compugen LTD. He has published over 70 manuscripts and won several awards and fellowships including the Clore, Fulbright, Rothschild, Alon and Krill.
It is widely accepted that, with the possible exception of rare and random somatic mutations, a genome remains unaltered throughout an organism’s life and serves as a template for exact RNA copies. However, endogenous and powerful means of creating inner genomic diversity is now known to exist: RNA editing, where ADAR proteins alter A-to-I leading to genomically encoded adenosines (A) to be read as guanosines (G). Its magnitude is unprecedented, with millions of RNA editing sites already identified in human. However, difficulties in detecting and measuring such events reliably, mean that the implications of this massive rewriting have hardly been studied at all.
Just as RNA editing events might drive adaptation in a way similar to genomic mutations, deregulated RNA editing might have an effect similar to that of disease-related genomic mutations. Altered editing could manifest as: changes in the level of recoding at known sites; creation of novel disease-specific recoding events; creation of novel editing-assisted splicing events; or modified editing patterns of circRNAs, miRNAs and their targets. These aberrant editing events could be viewed as a new class of non-heritable ‘RNA mutation’, which is not detectable by DNA sequencing. In our lab we developed a unique computational approach to detect RNA editing events and apply it across many biological conditions. As is the case with somatic genomic mutations, most newly introduced RNA mutations are likely to be passenger mutations, but a few may serve as driver mutations and represent novel candidates for therapeutic and diagnostic purposes. In our lab we found cases of altered editing in various cancer types, neurodegenerative and autoimmune diseases. Moreover, we have shown that that response for treatment, in several of the diseases, can be predicated from the editing landscape.