Two proteins essential for apolipoprotein B mRNA editing are expressed from a single gene through alternative splicing

Dance, G. S. C., Sowden, M. P., Cartegni, L., Cooper, E., Krainer, A. R., Smith, H. C. (April 2002) Two proteins essential for apolipoprotein B mRNA editing are expressed from a single gene through alternative splicing. Journal of Biological Chemistry, 277 (15). pp. 12703-12709. ISSN 0021-9258

URL: http://www.ncbi.nlm.nih.gov/pubmed/11815617

Abstract

Apolipoprotein B (apoB) mRNA editing involves site-specific deamination of cytidine to form uridine, resulting in the production of an in-frame stop codon. Protein translated from edited mRNA is associated with a reduced risk of atherosclerosis, and hence the protein factors that regulate hepatic apoB mRNA editing are of interest. A human protein essential for apoB mRNA editing and an eight-amino acid-longer variant of no known function have been recently cloned. We report that both proteins, henceforth referred to as ACF64 and ACF65, supported APOBEC-1 (the catalytic subunit of the editosome) equivalently in editing of apoB mRNA. They are encoded by a single 82-kb gene on chromosome 10. The transcripts are encoded by 15 exons that are expressed from a tissue-specific promoter minimally contained within the -0.33-kb DNA sequence. ACF64 and ACF65 mRNAs are expressed in both liver and intestinal cells in an approximate 1:4 ratio. Exon 11 is alternatively spliced to include or exclude 24 nucleotides of exon 12, thereby encoding ACF65 and ACF64, respectively. Recognition motifs for the serine/arginine-rich (SR) proteins SC35, SRp40, SRp55, and SF2/ASF involved in alternative RNA splicing were predicted in exon 12. Overexpression of these SR proteins in liver cells demonstrated that alternative splicing of a minigene-derived transcript to express ACF65 was enhanced 6-fold by SRp40. The data account for the expression of two editing factors and provide a possible explanation for their different levels of expression.

Item Type: Paper
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > RNA splicing
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > splicing factor
CSHL Authors:
Communities: CSHL labs > Krainer lab
Depositing User: Matt Covey
Date: April 2002
Date Deposited: 10 Dec 2013 15:11
Last Modified: 10 Dec 2013 15:11
Related URLs:
URI: http://repository.cshl.edu/id/eprint/28692

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