Thermodynamic Consequences of RNA Editing

Abstract

RNA editing involves the deletion or insertion of nucleotides. In double stranded RNA, enzymes known as adenosine deaminases that act on RNA (ADARs) catalyze adenosine deamination, the conversion of adenine (A) to inosine (I). RNA editing enhances the complexity offered by the genome. ADAR concentrations are high in the nervous system and defects in editing can cause severe neurological disorders by targeting receptors such as those for serotonin and glutamate. Editing is expected to destabilize the double stranded RNA by creating regions of unpaired bases in the helices. Preference and selectivity of editing sites by ADARs is not fully understood but is attributed to the associated changes in thermodynamic stability of the RNA. In this study, we are measuring changes in RNA stability for edited and unedited RNA constructs based on the serotonin and glutamate receptor sites. The neighboring base pairs of adenine that is being edited influence the RNA stability, as expected based on the nearest neighbor models. Optical melting studies were performed on several different oligoribonucleotides constructs containing adenine or inosine to calculate the thermodynamic changes in RNA under different conditions. The nearest neighbor parameters are calculated using multiple linear regression models. This work is funded by NSF grant MCB‐0621509 (NG).