Control of Apolipoprotein B mRNA Editing: Implications of mRNA Dynamics at Various Maturation Stages

Abstract

Apolipoprotein (apo) B mRNA editing is a genetic regulatory mechanism whereby nucleotide 6666 in apoB-100 mRNA is converted from a C to a U. The end result of this change is the creation of a premature stop codon so that the translation product of the edited (apoB-48) mRNA contains 2152 amino acid residues instead of 4536 residues in the product (apoB-100) encoded by the unedited mRNA. ApoB mRNA editing is a post-transcriptional process that is expressed in a tissue-specific manner. Here we present a model for the control of apoB mRNA editing. The three variables in the model include editing activity, apoB mRNA transcription rate and mRNA degradation rate at various maturation stages for the mRNA, and a simple formula can be used to quantify the degree of apoB mRNA editing with respect to these variables at different apoB mRNA maturation stages. Time-dependent equations were solved numerically. Using this model it can be shown that, in addition to editing activity, the degradation kinetics of apoB mRNA can also serve as an efficient modulator of the degree of editing. The rate of apoB mRNA transcription has a transient effect on the degree of editing; varying the apoB mRNA degradation constant tends to change the degree of editing only at specific maturation stage. This model can render some previously proposed hypothesis (e.g. coupling of mRNA editing to splicing/polyadenylation) unnecessary and provides a rational basis for the design of experiments on specific aspects of apoB mRNA editing in the future; it may also be applicable to other types of RNA editing.