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Journal of Lipid Research, Vol 36, 414-428, Copyright © 1995 by Lipid Research, Inc.
T Funahashi, F Giannoni, AM DePaoli, SF Skarosi and NO Davidson
Apolipoprotein B (apoB) mRNA editing, a posttranscriptional site- specific
cytidine deamination reaction, is mediated by a protein complex of which
the catalytic component (REPR) has recently been cloned. REPR mRNA was
demonstrated by RNase protection at highest abundance in small intestine
and colon but the transcript was detectable in all tissues examined
including kidney, spleen, lung, liver, and ovary. ApoB mRNA was found
predominantly in the liver and small intestine but low levels were detected
in all adult tissues examined and found to be variably (29-86% TAA) edited.
In addition, S100 extracts prepared from spleen and kidney were competent
to edit an apoB RNA template in vitro, suggesting that the entire apoB mRNA
editing complex is present and functionally active in these tissues. In
situ hybridization demonstrated REPR mRNA to be distributed along the
entire villus-crypt axis, while apoB mRNA distribution did not extend into
the crypts. In the liver, both apoB and REPR mRNA were detected in all
cells of the hepatic lobule without an apparent gradient of expression.
REPR mRNA was found in the red pulp of the spleen and in the superficial
crypt cells of the colon. This distribution of REPR mRNA was recapitulated
by immunocytochemical localization of the protein within these tissues.
Finally, the developmental and nutritional modulation of REPR was examined
in relation to endogenous apoB mRNA editing. Small intestinal apoB mRNA
editing was found to undergo a developmentally regulated increase beginning
at gestational day 20, preceding a developmental increase in REPR mRNA
abundance. Additionally, hepatic and kidney apoB mRNA editing both revealed
a temporal dissociation from alterations in REPR mRNA abundance. By
contrast, adult rats subjected to fasting and refeeding a high carbohydrate
diet, demonstrated concordant modulation of endogenous apoB mRNA editing
and REPR mRNA abundance (r = 0.92, P < 0.001). Taken together, the data
demonstrate that REPR and other components of the rat apoB mRNA editing
complex are widely distributed and undergo distinct developmental and
metabolic regulation that interact to regulate apoB mRNA editing in a
tissue-specific manner.
ARTICLES
Tissue-specific, developmental and nutritional regulation of the gene encoding the catalytic subunit of the rat apolipoprotein B mRNA editing enzyme: functional role in the modulation of apoB mRNA editing
Department of Medicine, University of Chicago, IL 60637, USA.
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