The multifaceted roles of RNA binding in APOBEC cytidine deaminase functions

Abstract

Cytidine deaminases have important roles in the regulation of nucleoside/deoxynucleoside pools for DNA and RNA synthesis. The APOBEC family of cytidine deaminases (named after the first member of the family that was described, Apolipoprotein B mRNA Editing Catalytic Subunit 1, a.k.a. APOBEC1 or A1) is a fascinating group of mutagenic proteins that use RNA and single stranded DNA (ssDNA) as substrates for their cytidine or deoxycytidine deaminase activities. APOBEC proteins and base-modification nucleic acid editing have been the subject of numerous publications, reviews and speculation. These proteins play diverse roles in host cell defense, protecting cells from invading genetic material, enabling the acquired immune response to antigens and changing protein expression at the level of the genetic code in mRNA or DNA. The amazing power these proteins have for interphase cell functions relies on structural and biochemical properties that are beginning to be understood. At the same time, the substrate selectivity of each member in the family and their regulation remains to be elucidated. This review of the APOBEC family will focus on an open question in regulation, namely what role the interactions of these proteins with RNA have in editing substrate recognition or allosteric regulation of DNA mutagenic and host defense activities.

STRIPE2 Encodes a Putative dCMP Deaminase that Plays an Important Role in Chloroplast Development in Rice

“…uid¼cd00786&seltype¼1) can be divided into four subfamilies, including riboflavin deaminase, cytidine deaminase, dCMP deaminase and nucleoside deaminase. In mammals, the cytidine deaminase such as APOBEC-1 is responsible for C-to-U editing of the apolipoprotein mRNA (Prohaska et al, 2014). In higher plants, RNA editing is a post-transcriptional process of altering a specific nucleotide C to U (and less frequently, from U to C) in organelle mRNAs.…”

Post-transcriptional regulation of LINE-1 retrotransposition by AID/APOBEC and ADAR deaminases

“…It would be of great interest to test whether this is true for all the family members. In fact, almost every member of the AID/APOBEC family interacts with RNA molecules even if they are not substrates for deamination, and this interaction may influence their function (Prohaska et al 2014;Smith 2016). …”

Identification of DNA cleavage- and recombination-specific hnRNP cofactors for activation-induced cytidine deaminase

“…Although most of these related proteins are predicted to be involved in cytidine deamination, their targets and the molecular mechanisms are not fully elucidated (15). The best-characterized AID-like enzyme is APOBEC1, an RNA-editing enzyme that catalyzes the site-specific deamination of C to U at position 6666 of the apolipoprotein B-100 (APO B-100) mRNA, generating a premature stop codon (16)(17)(18). The edited mRNA, referred to as "APOB-48," encodes the triglyceride carrier protein, a truncated product of the LDL carrier protein, which is encoded by APO B-100 mRNA.…”