Cloning of an Apobec-1-binding Protein That Also Interacts with Apolipoprotein B mRNA and Evidence for Its Involvement in RNA Editing

Abstract

Apolipoprotein (apo)B mRNA editing is mediated by a multiprotein editosome complex. Apobec-1 is the catalytic component of this complex, but other proteins involved in editing have not been identified. We used the yeast two-hybrid system to identify an apobec-1-interacting protein, ABBP-1. ABBP-1 contains 331 amino acid residues and is identical to a previously reported human type A/B hnRNP except for a 47-residue insertion at its C-terminal region. It contains typical RNP motifs at its N-terminal half and glycine-rich motifs in the C-terminal region. Northern blot analysis indicates that ABBP-1 mRNA is distributed in multiple human tissues. By deletion analysis, we mapped the apobec-1-binding region to the glycine-rich domain. ABBP-1 also binds to apoB mRNA transcripts around the editing site and can be UV-cross-linked to them in vitro. Immnodepletion of ABBP-1 from an active apoB mRNA editing tissue extract inhibits its editing activity. Down-regulation of ABBP-1 in an apobec-1-expressing HepG2 cell line by transfection with an antisense ABBP-1 cDNA construct leads to inhibition of endogenous apoB mRNA editing. We conclude that ABBP-1 is an apobec-1-interacting protein that may play an important role in apoB mRNA editing.

Genetic and hormonal control of hepatic steatosis in female and male mice

“…These ubiquitination complexes have been shown to play a role in hepatic lipid accumulation (45). Heterogenous nuclear ribonucleoprotein A/B (Hnrnpab) has been shown to play a role in apolipoprotein B mRNA editing in a cultured human hepatoma cell line (46). Apolipoprotein B is an important component of lipoproteins secreted from the liver.…”

Commitment of apolipoprotein B RNA to the splicing pathway regulates cytidine-to-uridine editing-site utilization

“…The components of the minimal editosome from defined in itro system analyses are APOBEC-1 as a homodimeric cytidine deaminase [28] bound to the auxiliary protein ACF\ASP that serves as the editing-site recognition factor through its mooringsequence-selective RNA-binding activity [30,31]. Several other auxiliary protein candidates have also been described that had binding affinities for APOBEC-1 and\or apoB mRNA and that demonstrated the ability to modulate editing efficiency [23,24,26,31,33,34,37,38]. Although, under biological conditions, editing occurs only in the nucleus [8,9], nuclear and cytoplasmic distributions have been described for both APOBEC-1 and ACF [9,52,53].…”

“…Consistent with this possibility of communication between the spliceosome and editosome is the finding that several proteins that have a role in RNA structure and\or splicing have also been implicated in RNA editing as auxiliary factors. These include hnRNP C, hnRNP D, APOBEC-1-binding protein (which has homology with hnRNP A and B) and KSRP, a protein involved in alternative splice site utilization [31,[36][37][38].…”

“…Editingsite specificity and RNA editing activity are imparted upon APOBEC-1 through its interactions with ACF\ASP [30,31] and potentially other auxiliary proteins which bind to APOBEC-1 and\or apoB mRNA and modulate the efficiency of the editing reaction [23,24,[33][34][35]. In terms of the potential effect of premRNA splicing on apoB mRNA editing, some of the auxiliary proteins implicated in apoB mRNA editing, including heterogeneous ribonucleoprotein (hnRNP) C, hnRNP D, APOBEC-1-binding protein and KSRP (KH type splicing regulatory protein) have a role in pre-mRNA splicing and\or hnRNP structure [31,[36][37][38]. Tissue-specific heterogeneity in auxiliary protein expression and function [16,27], and the widespread expression of the auxiliary proteins, even in cells that lack apobec-1 or apoB mRNA [23,24,26,30,33], has suggested an additional role(s) for these auxiliary proteins.…”

A DnaJ Protein, Apobec-1-binding Protein-2, Modulates Apolipoprotein B mRNA Editing

“…Two of these clones isolated from a human placenta library were reported by us as ABBP-1 (27) and GRY-RBP (28). Another clone that was obtained from a human liver library (CLONTECH, Inc.) contains a partial ABBP-2 cDNA.…”