Quantitation of endogenous liver apolipoprotein B mRNA editing

Backus, John W.; Eagleton, Matthew J.; Harris, Stanley G.; Sparks, Charles E.; Sparks, Janet D.; Smith, Harold C.

doi:10.1016/0006-291x(90)92121-f

Cited by 12 publications

(5 citation statements)

References 15 publications

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“…ApoB mRNA editing was quantified by the poisoned primer extension assay as previously described [33] on apoB cDNA amplified from 2 μg of total RNA isolated from the liver of Ob/Ob and C57Bl/6J mice as described above.…”

Section: Methodsmentioning

confidence: 99%

Metabolic regulation of APOBEC-1 Complementation Factor trafficking in mouse models of obesity and its positive correlation with the expression of ApoB protein in hepatocytes

Galloway¹,

Ashton²,

Sparks³

et al. 2010

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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APOBEC-1 Complementation Factor (ACF) is an RNA-binding protein that interacts with apoB mRNA to support RNA editing. ACF traffics between the cytoplasm and nucleus. It is retained in the nucleus in response to elevated serum insulin levels where it supports enhanced apoB mRNA editing. In this report we tested whether ACF may have the ability to regulate nuclear export of apoB mRNA to the sites of translation in the cytoplasm. Using mouse models of obesity-induced, insulin resistance and primary hepatocyte cultures we demonstrated that both nuclear retention of ACF and apoB mRNA editing were reduced in the livers of hyperinsulinemic obese mice relative to lean controls. Coincident with an increase in the recovery of ACF in the cytoplasm was an increase in the proportion of total cellular apoB mRNA recovered in cytoplasmic extracts. Cytoplasmic ACF from both lean controls and obese mouse livers was enriched in endosomal fractions associated with apoB mRNA translation and ApoB lipoprotein assembly. Inhibition of ACF export to the cytoplasm resulted in nuclear retention of apoB mRNA and reduced both intracellular and secreted ApoB protein in primary hepatocytes. The importance of ACF for modulating ApoB was supported by the finding that RNAi knockdown of ACF reduced ApoB secretion. An additional discovery from this study was the finding that leptin is a suppressor ACF expression. Dyslipidemia is a common pathology associated with insulin resistance that is in part due to the loss of insulin controlled secretion of lipid in ApoB-containing very low density lipoproteins. The data from animal models suggested that loss of insulin regulated ACF trafficking and leptin regulated ACF expression may make an early contribution to the overall pathology associated with very low-density lipoprotein secretion from the liver in obese individuals.

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Section: Methodsmentioning

confidence: 99%

Metabolic regulation of APOBEC-1 Complementation Factor trafficking in mouse models of obesity and its positive correlation with the expression of ApoB protein in hepatocytes

Galloway¹,

Ashton²,

Sparks³

et al. 2010

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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“…Cytidine 6666 (C6666) of the mammalian apolipoprotein B (apoB) mRNA is edited to uridine by deamination (1) producing a codon change from glutamine to STOP (2). Unedited and edited mRNAs are translated into full length apoB100 and a truncated variant (apoB48) respectively (2)(3)(4)(5), the latter of which is associated with a reduced risk of atherogenic diseases. ApoB mRNA editing requires a 26 nt tripartite motif consisting of the mooring sequence and spacer element downstream of C6666, and a regulatory element upstream of C6666 (6)(7)(8)(9).…”

Section: Introductionmentioning

confidence: 99%

APOBEC-1 dependent cytidine to uridine editing of apolipoprotein B RNA in yeast

Dance

Sowden²,

Yang³

et al. 2000

Nucleic Acids Research

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Cytidine to uridine editing of apolipoprotein B (apoB) mRNA requires the cytidine deaminase APOBEC-1 as well as a tripartite sequence motif flanking a target cytidine in apoB mRNA and an undefined number of auxiliary proteins that mediate RNA recognition and determine site-specific editing. Yeast engineered to express APOBEC-1 and apoB mRNA supported editing under conditions of late log phase growth and stationary phase. The cis -acting sequence requirements and the intracellular distribution of APOBEC-1 in yeast were similar to those described in mammalian cells. These findings suggest that auxiliary protein functions necessary for the assembly of editing complexes, or 'editosomes', are expressed in yeast and that the distribution of editing activity is to the cell nucleus.

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“…In rat liver, apoBL production and secretion are also developmentally regulated, while the apoBH phenotype is maintained (1,(8)(9)(10)(11)(12)(13). In adult rat liver, 40-50%o of the total apoB mRNA is edited (13,14).…”

mentioning

confidence: 99%

In vitro apolipoprotein B mRNA editing: identification of a 27S editing complex.

Smith

Kuo

Backus

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

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Specific apolipoprotein B (apoB) mRNA editing can be performed in vitro on apoB RNA substrates. Native gels and glycerol gradient sedimentation have been used to determine the physical properties of the in vitro editing activity in rat liver cytosolic S100 extracts. ApoB RNA substrates were progressively assembled as 27S complexes for 3 hr with similar kinetics as seen for the accumulation of edited RNA. Assembly was not observed on RNAs from apoB deletion constructs that did not support editing. The 27S complex contained both edited and unedited RNA sequences. Inhibition of 27S complex assembly by vanadyl-ribonucleoside complexes was accompanied by inhibition of editing. Based on these data, we propose that the 27S complex is the in vitro "editosome." A "mooring sequence" model for RNA recognition and editosome assembly has been proposed involving RNA sequences flanking the edited nucleotide.

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Quantitation of endogenous liver apolipoprotein B mRNA editing

Cited by 12 publications

References 15 publications

Metabolic regulation of APOBEC-1 Complementation Factor trafficking in mouse models of obesity and its positive correlation with the expression of ApoB protein in hepatocytes

Metabolic regulation of APOBEC-1 Complementation Factor trafficking in mouse models of obesity and its positive correlation with the expression of ApoB protein in hepatocytes

APOBEC-1 dependent cytidine to uridine editing of apolipoprotein B RNA in yeast

In vitro apolipoprotein B mRNA editing: identification of a 27S editing complex.

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