Cloning and mutagenesis of the rabbit ApoB mRNA editing protein. A zinc motif is essential for catalytic activity, and noncatalytic auxiliary factor(s) of the editing complex are widely distributed.

Yamanaka, Shinya; Poksay, Karen S.; Balestra, Maureen E.; Zeng, Guo-Qing; Innerarity, Thomas L.

doi:10.1016/s0021-9258(17)31865-3

Cited by 105 publications

(8 citation statements)

References 43 publications

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“…4, lanes 1 and 2). Promiscuous editing of the 5′ cytidine C6655 was readily apparent (lane 2) but only trace levels or no promiscuous editing of the 3′ cytidines C6675, C6702 and 6724 could be demonstrated (lanes [3][4][5][6][7][8]. These data demonstrated that the in vitro system recapitulates site specific and promiscuous apoB RNA editing in cells under conditions of both normal and over-expressed APOBEC-1.…”

Section: Rnas Lacking Tandem Ugau Motifs 3′ Of the Mooring Sequence Do Not Support Promiscuous Editing Of 5′ Cytidines In Mcardle Cellsmentioning

confidence: 87%

“…Auxiliary protein factors are just beginning to be characterized from the point of view of the number of proteins involved and their function (18)(19)(20)24,30,39,40). It is currently clear that APOBEC-1 cannot edit apoB mRNA without these factors and that the occurrence of auxiliary factors in nature is not restricted to cells that express apoB mRNA or APOBEC-1 (5,21,25).…”

Section: Discussionmentioning

confidence: 99%

“…Apolipoprotein (ApoB) mRNA editing alters a genomically encoded glutamine codon (CAA) at position 2153 to a STOP codon (UAA) in RNA through site-specific cytidine deamination (1,2). The process is mediated by the 27 kDa cytidine deaminase, APOBEC-1 (apoB editing catalytic sub-unit 1), which has been cloned from human, rat, rabbit and mouse (3)(4)(5)(6). The enzyme functions as a homodimer (6,7), that binds to RNA weakly and non-specifically (8,9).…”

Section: Introductionmentioning

confidence: 99%

“…To edit apoB mRNA, APOBEC-1 requires auxiliary proteins for editosome assembly and efficient site-specific editing activity (4,(15)(16)(17)(18)(19)(20). The auxiliary proteins have a widespread distribution and can be demonstrated in extracts from cells that do not synthesize apoB mRNA (5,21). These factors can interact specifically with APOBEC-1 and some may bind apoB mRNA (18)(19)(20).…”

Section: Introductionmentioning

confidence: 99%

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Apolipoprotein B RNA sequence 3' of the mooring sequence and cellular sources of auxiliary factors determine the location and extent of promiscuous editing

Sowden

Eagleton

Smith

1998

Nucleic Acids Research

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Apolipoprotein B (apoB) RNA editing involves a cytidine to uridine transition at nucleotide 6666 (C6666) 5' of an essential cis -acting 11 nucleotide motif known as the mooring sequence. APOBEC-1 (apoB editing catalytic sub-unit 1) serves as the site-specific cytidine deaminase in the context of a multiprotein assembly, the editosome. Experimental over-expression of APOBEC-1 resulted in an increased proportion of apoB mRNAs edited at C6666, as well as editing of sites that would otherwise not be recognized (promiscuous editing). In the rat hepatoma McArdle cell line, these sites occurred predominantly 5' of the mooring sequence on either rat or human apoB mRNA expressed from transfected cDNA. In comparison, over-expression of APOBEC-1 in HepG2 (HepG2-APOBEC) human hepatoma cells, induced promiscuous editing primarily 5' of the mooring sequence, but sites 3' of the C6666 were also used more efficiently. The capacity for promiscuous editing was common to rat, rabbit and human sources of APOBEC-1. The data suggested that differences in the distribution of promiscuous editing sites and in the efficiency of their utilization may reflect cell-type-specific differences in auxiliary proteins. Deletion of the mooring sequence abolished editing at the wild type site and markedly reduced, but did not eliminate, promiscuous editing. In contrast, deletion of a pair of tandem UGAU motifs 3' of the mooring sequence in human apoB mRNA selectively reduced promiscuous editing, leaving the efficiency of editing at the wild type site essentially unaffected. ApoB RNA constructs and naturally occurring mRNAs such as NAT-1 (novel APOBEC-1 target-1) that lack this downstream element were not promiscuously edited in McArdle or HepG2 cells. These findings underscore the importance of RNA sequences and the cellular context of auxiliary factors in regulating editing site utilization.

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Section: Rnas Lacking Tandem Ugau Motifs 3′ Of the Mooring Sequence Do Not Support Promiscuous Editing Of 5′ Cytidines In Mcardle Cellsmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Apolipoprotein B RNA sequence 3' of the mooring sequence and cellular sources of auxiliary factors determine the location and extent of promiscuous editing

Sowden

Eagleton

Smith

1998

Nucleic Acids Research

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“…Apolipoprotein B mRNA-editing enzyme catalytic polypeptide 1 Transgenic mice and rabbits expressing rabbit apolipoprotein B mRNA-editing enzyme catalytic polypeptide 1, APOBEC-1, were generated by Yamanaka and colleagues (39) to determine whether hepatic expression would reduce plasma LDL cholesterol concentrations. A fulllength cDNA fragment of rabbit APOBEC-1 was microinjected into fertilized oocytes of NZW rabbits (40), and transgene copy number was estimated by Southern blot analysis using the endogenous rabbit APOBEC-1 gene as a control. Two transgenic rabbit founders were identified, one having one copy of the APOBEC-1 transgene and the other 17 copies.…”

Section: Lipid Enzyme Transgenes Expressed In the Nzw Rabbitmentioning

confidence: 99%

Transgenic rabbits as models for atherosclerosis research

Brousseau¹,

Hoeg²

1999

Journal of Lipid Research

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Several characteristics of the rabbit make it an excellent model for the study of lipoprotein metabolism and atherosclerosis. New Zealand White (NZW) rabbits have low plasma total cholesterol concentrations, high cholesteryl ester transfer protein activity, low hepatic lipase (HL) activity, and lack an analogue of human apolipoprotein (apo) A-II, providing a unique system in which to assess the effects of human transgenes on plasma lipoproteins and atherosclerosis susceptibility. Additionally, rabbit models of human lipoprotein disorders, such as the Watanabe Heritable Hyperlipidemic (WHHL) and St. Thomas' Hospital strains, models of familial hypercholesterolemia and familial combined hyperlipidemia, respectively, allow for the assessment of candidate genes for potential use in the treatment of dyslipoproteinemic patients. To date, transgenes for human apo(a), apoA-I, apoB, apoE 2 , apoE 3 , HL, and lecithin:cholesterol acyltransferase (LCAT), as well as for rabbit apolipoprotein B mRNA-editing enzyme catalytic polypeptide 1 (APOBEC-1), have been expressed in NZW rabbits, whereas only those for human apoA-I and LCAT have been introduced into the WHHL background. All of these transgenes have been shown to have significant effects on plasma lipoprotein concentrations. In both NZW and WHHL rabbits, human apoA-I expression was associated with a significant reduction in the extent of aortic atherosclerosis, which was similarly the case for LCAT in rabbits having at least one functional LDL receptor allele. Conversely, expression of apoE 2 in NZW rabbits caused increased susceptibility to atherosclerosis. These studies provide new insights into the mechanisms responsible for the development of atherosclerosis, emphasizing the strength of the rabbit model in cardiovascular disease research. -Brousseau, M. E., and J. M. Hoeg. Transgenic rabbits as models for atherosclerosis research.

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Editing of the GLuR-B ion channel RNA in vitro by recombinant double-stranded RNA adenosine deaminase.

et al. 1996

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Double‐stranded RNA (dsRNA)‐specific adenosine deaminase (DRADA) has been implicated as an enzyme responsible for the editing of RNA transcripts encoding glutamate‐gated ion channel subunits (GLuR) in brain. In one case, the editing alters the gene‐encoded glutamine (Q) to an arginine (R) located within the channel‐forming domain of the alpha‐amino‐3‐hydroxy‐5‐methyl‐isoxazole‐4‐propionic acid (AMPA) receptor subunit GLuR‐B. The result of editing at this site, called the ‘Q/R’ site, is a profound alteration of the Ca2+ permeability of the GLuR channel. Using recombinantly expressed DRADA proteins, we now demonstrate in vitro that DRADA is indeed involved in editing of the GLuR‐B RNA. In addition to the formation of an RNA duplex structure involving exon and intron sequences, Q/R site‐selective editing by DRADA also requires a cofactor protein(s) commonly present even in non‐neuronal cells. The accuracy and efficiency of this RNA editing system appear to be determined by the quantitative balance between DRADA, cofactor and substrate GLuR‐B RNA.

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Cloning and mutagenesis of the rabbit ApoB mRNA editing protein. A zinc motif is essential for catalytic activity, and noncatalytic auxiliary factor(s) of the editing complex are widely distributed.

Cited by 105 publications

References 43 publications

Apolipoprotein B RNA sequence 3' of the mooring sequence and cellular sources of auxiliary factors determine the location and extent of promiscuous editing

Apolipoprotein B RNA sequence 3' of the mooring sequence and cellular sources of auxiliary factors determine the location and extent of promiscuous editing

Transgenic rabbits as models for atherosclerosis research

Editing of the GLuR-B ion channel RNA in vitro by recombinant double-stranded RNA adenosine deaminase.

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