Mouse and Other Rodent Models of C to U RNA Editing
Substitutional RNA editing represents an important posttranscriptional enzymatic pathway for increasing genetic plasticity by permitting production of different translation products from a single genomically encoded template. One of the best-characterized examples in mammals is C to U deamination of the nuclear apolipoprotein B (apoB) mRNA. ApoB mRNA undergoes a single, site-specific cytidine deamination event yielding an edited transcript that results in tissue-specific translation of two distinct isoforms, referred to as apoB100 and apoB48. Tissue- and site-specific cytidine deamination of apoB mRNA is mediated by an incompletely characterized holoenzyme containing a minimal core complex consisting of an RNA-specific cytidine deaminase, Apobec-1 and a requisite cofactor, apobec-1 complementation factor (ACF). The underlying biochemical and genetic mechanisms regulating tissue-specific apoB mRNA editing have been accelerated through development and characterization of physiological rodent models as well as knockout and transgenic animal strains.
Key wordsLipid metabolism RNA editing Apobec-1 Hepatocytes Hormonal regulation Diet Primer extension Subcellular distribution
Work cited in this review was supported by grants from the National Institutes of Health (HL-38180, DK-56260, DK-52574) to NOD. The authors are deeply grateful to Susan Kennedy and Jianyang Luo for assistance with the murine models quoted in this review.
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