Chapter 19 - Mouse Models as Tools to Explore Cytidine-to-Uridine RNA Editing

Abstract

RNA editing is a process through which the nucleotide sequence specified in the genomic template is modified to produce a different nucleotide sequence in the transcript. RNA editing is an important mechanism of genetic regulation that amplifies genetic plasticity by allowing the production of alternative protein products from a single gene. There are two generic classes of RNA editing in nuclei, involving enzymatic deamination of either C-to-U or A-to-I nucleotides. The best characterized example of C-to-U RNA editing is that of apolipoprotein B (apoB), which is mediated by a holoenzyme that contains a minimal core composed of an RNA-specific cytidine deaminase apobec-1, and its cofactor apobec-1 complementation factor (ACF). C-to-U editing of apoB RNA generates two different isoforms--apoB100 and apoB48--from a single transcript. Both are important regulators of lipid transport and metabolism, and are functionally distinct. C-to-U apoB RNA editing is regulated by a range of factors including developmental, nutritional, environmental, and metabolic stimuli. Rodent models have provided a tractable system in which to study the effects of such stimuli on lipid metabolism. In addition, both transgenic and gene knockout experiments have provided important insights into gain and loss of function approaches for studying C-to-U RNA editing in a murine background.