Extract-specific heterogeneity in high-order complexes containing apolipoprotein B mRNA editing activity and RNA-binding proteins.

Harris, Stanley G.; Sabio, Ivan; Mayer, E J; Steinberg, M F; Backus, John W.; Sparks, Janet D.; Sparks, Charles E.; Smith, Harold C.

doi:10.1016/s0021-9258(18)53186-0

Cited by 102 publications

(11 citation statements)

References 33 publications

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“…Although we have reported cytoplasmic localization of APOBEC-1 and ACF [9,52], there is no precedent for them to form active editosomes in the cytoplasm in i o or for there to be cytoplasmic editing when APOBEC-1 expression was under biological regulation [9]. Specifically, cytoplasmic APOBEC-1 and ACF existed within an inactive 60 S complex that only became an activated 27 S editosome in the nucleus [11,22]. The possibility of cytoplasmic editing was shown in studies in which an enhanced editing efficiency was observed upon IVS-apoB chimaeric RNA by a cytoplasmically ' tethered ' chicken muscle pyruvate kinase-APOBEC-1 fusion protein [9].…”

Section: Discussionmentioning

confidence: 96%

“…It is well established that a sequence element consisting of three proximal components (enhancer, spacer and mooring sequence) com-prise the cis-acting sequences required for efficient site-specific editing of C6666 in apoB mRNA [11][12][13][14][15]45]. A multiple protein editosome catalyses and regulates editing of C'''' [11,22,26]. 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].…”

Section: Discussionmentioning

confidence: 99%

“…Cytidine deamination in itro and in i o required a multiprotein complex or ' editosome ' [22][23][24][25]. Editosome assembly in cells [22,26] or in itro [11,15,22,27] required a complex protein composition with an aggregate size of 27 S. Minimally, in itro editing activity required a homodimer of APOBEC-1 (catalytic subunit for cytidine-to-uridine editing of apolipoprotein B mRNA-1), the zinc-dependent catalytic subunit of cytidine deaminase [28,29] and a 65 kDa RNA binding protein, ACF\ASP (APOBEC-1 complementation factor\APOBEC-1 stimulatory protein) [30,31]. APOBEC-1 demonstrated a weak and non-specific RNA binding activity to AU-rich apoB sequences [32] and alone could not edit apoB mRNA.…”

Section: Introductionmentioning

confidence: 99%

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

Sowden

Smith

2001

Biochem. J.

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A tripartite motif located in the centre of the 7.5 kb exon 26 of apolipoprotein B (apoB) mRNA directs editosome assembly and site-specific cytidine-to-uridine editing at nucleotide 6666. apoB mRNA editing is a post-transcriptional event, occurring primarily at the time exon 26 is spliced or at a time after splicing, but before nuclear export. We show, through reporter RNA constructs, that RNA splice sites suppress editing of precursor RNAs when placed proximal or distal to the editing site. Processed RNAs were edited more efficiently than precursor RNAs. Mutation of both the splice donor and acceptor sites was necessary for RNAs to be edited efficiently. The results suggested that commitment of pre-mRNA to the splicing and/or nuclear-export pathways may play a role in regulating editing-site utilization. The HIV-1 Rev-Rev response element ('RRE') interaction was utilized to uncouple the commitment of precursor RNAs to the spliceosome assembly pathway and associated nuclear-export pathway. Under these conditions, unspliced reporter RNAs were edited efficiently. We propose that pre-mRNA passage through the temporal or spatial restriction point where they become committed to spliceosome assembly contributes regulatory information for subsequent editosome activity.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Sowden

Smith

2001

Biochem. J.

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“…The analysis to this point has evaluated APOBEC-1 over-expression in the context of auxiliary proteins from McArdle cells. Given the absolute requirement of auxiliary factors for APOBEC-1 editing activity (4,(15)(16)(17)(18)(19)(20) the characteristics of promiscuous editing were evaluated in the context of auxiliary factors from human HepG2 cells. HepG2 cells transcribed apoB RNA but were incapable of significant RNA editing due to their impaired ability to express apobec-1 mRNA (Fig.…”

Section: Promiscuous Editing In Human Liver Cells Over-expressing Rat Apobec-1mentioning

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).…”

Section: Introductionmentioning

confidence: 99%

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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APOBEC‐1‐mediated RNA editing

Blanc

Davidson

2010

WIREs Mechanisms of Disease

107

110

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RNA editing defines a molecular process by which a nucleotide sequence is modified in the RNA transcript and results in an amino acid change in the recoded message from that specified in the gene. We will restrict our attention to the type of RNA editing peculiar to mammals, i.e., nuclear C to U RNA editing. This category of RNA editing contrasts with RNA modifications described in plants, i.e., organellar RNA editing (reviewed in Ref 1). Mammalian RNA editing is genetically and biochemically classified into two groups, namely insertion‐deletional and substitutional.2 Substitutional RNA editing is exclusive to mammals, again with two types reported, namely adenosine to inosine and cytosine to uracil (C to U).3, 4 This review will examine mammalian C to U RNA editing of apolipoproteinB (apoB) RNA and the role of the catalytic deaminase Apobec‐1.5, 6 We will speculate on the functions of Apobec‐1 beyond C to U RNA editing as implied from its ability to bind AU‐rich RNAs and discuss evidence that dysregulation of Apobec‐1 expression might be associated with carcinogenesis through aberrant RNA editing or altered RNA stability. Copyright © 2010 John Wiley & Sons, Inc. This article is categorized under: Biological Mechanisms > Regulatory Biology

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Extract-specific heterogeneity in high-order complexes containing apolipoprotein B mRNA editing activity and RNA-binding proteins.

Cited by 102 publications

References 33 publications

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

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

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

APOBEC‐1‐mediated RNA editing

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