Deaminase-Dependent and Deaminase-Independent Functions of APOBEC1 and APOBEC1 Complementation Factor in the Context of the APOBEC Family
Harold C. Smith
from: RNA Editing: Current Research and Future Trends (Edited by: Stefan Maas). Caister Academic Press, U.K. (2013)
Two decades of research revealed the mechanism for site-specific, apolipoprotein B (apoB) mRNA C to U editing and its developmental and metabolic regulation. The field began to lose momentum while many open questions remained. This was due to perceived impasses in translational research endpoints: (1) liver is the most significant organ in the metabolism of cholesterol- and triglyceride-rich lipoproteins and despite active and regulated hepatic editing in rodent models, human liver does not express the cytidine deaminase APOBEC1 required for apoB mRNA editing. (2) Mammals express APOBEC1 in their small intestines where 100% of the apoB mRNA is edited in adults but this activity is constitutive. (3) Expression of APOBEC1 is not essential for life in mice. In the past few years there has been a resurgence in interest because: (1) APOBEC1 edits the 3' UTRs of multiple mRNAs and either alone or together with its RNA-binding cofactor, A1CF, may regulate mRNA stability and translation in diverse tissues. (2) A1CF is required for embryological development, acting through a mechanism that may be unrelated to APOBEC1. (3) Discovery of dC to dU DNA mutational activity by APOBEC1 raises new questions of its oncogenic potential. This review will consider past and current discoveries relative to the exciting new research opportunities in the field read more ...