Nucleotide sequence of cloned cDNA of human apolipoprotein A-l

Abstract

ApoA-I is the major human HDL apoprotein. By oligonucleotide hybridization, we have isolated 5 dscDNA clones to human hepatic apo A-I mRNA. One of these clones (pAl-3) was completely sequenced. It has 878 bp plus a poly A tail of 48 and includes all the coding and 3’–untranslated regions of the mRNA and part of the 5’–untranslated region. It predicts a peptide sequence of 267 amino acids (including the 24 amino acid prepropeptides) which is very similar to the sequence reported by Brewer et al ., (1978) Biochem. Biophys. Res. Commun. 80:623-630. The predicted signal peptide sequence is highly homologous to the rat apoA–I signal peptide. There Is no evidence for any internally repeated segments in apoA–I either at the amino acid or at the DNA level. Using pAl–3 as a probe, we have detected on Northern gels apo A-I mRNA sequences of ˜1100 nucleotides in human hepatic and baboon hepatic and intestinal RNAs, but not in RNAs from baboon skeletal muscle, kidney or spleen. The demonstration of apo A-I mRNA sequences in specific organs is important to our concept of “reverse cholesterol transport”.