Nucleic Acids Research, Vol 26, Issue 7 1644-1652, Copyright © 1998 by Oxford University Press
MP Sowden, MJ Eagleton and HC Smith
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.
ARTICLES
Apolipoprotein B RNA sequence 3' of the mooring sequence and cellular sources of auxiliary factors determine the location and extent of promiscuous editing
Department of Biochemistry and Biophysics, University of Rochester School of Medicine and Dentistry, Box 712, 601 Elmwood Avenue, Rochester, NY 14642, USA.
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