Expression of apolipoprotein B mRNAs encoding higher- and lower-molecular weight isoproteins in rat liver and...

Two B apolipoproteins (apo) are present in human plasma, designated apoB-100 and apoB-48, and represent translational products from mature apoB mRNAs that differ by a single base. Either the glutamine codon encoded by the single-copy apoB gene at nucleotide 6666 is transcribed and translated to produce apoB-100 or an RNA-editing mechanism substitutes a uracil for cytosine, altering this glutamine codon (CAA) to a stop codon (UAA), prematurely terminating translation to produce apoB-48. In the present report, editing of rat apoB transcripts was evaluated by amplification of RNA with the polymerase chain reaction by use of primers based on the apoB cDNA cloned from a rat liver cDNA library. The combined results of this study show that (i) a single copy of the apoB gene exists in the rat; (ii) the rat apoB gene encodes only the glutamine codon for the synthesis of apoB of higher molecular weight (apoBH); (iii) rat apoB transcripts undergo RNA editing; (iv) apoBH and apoB of lower molecular weight (apoBL) in the rat represent structural equivalents of apoB-100 and apoB-48 in humans, respectively; (v) RNA editing occurs in both the liver and intestine of the rat; (vi) rat hepatic apoB RNA is more extensively edited than is human hepatic apoB RNA, which is consistent with the marked increase in apoBL secretion by the rat liver when compared with human; and (vii) the definitive identification of apoBH mRNA as well as apoBL mRNA in the rat intestine provides a mechanism for the biosynthesis of both apoBH and apoBL by the rat intestine.