TY - JOUR
T1 - Alternative splicing in lecithin:cholesterol acyltransferase mRNA
T2 - An evolutionary paradigm in humans and great apes
AU - Miller, Michael
AU - Zeller, Karen
N1 - Funding Information:
We thank the Yerkes Regional Primate Center and the Department of Pathology at the National Zoo in Washington, DC (a division of the Smithsonian Institution) for supplying primate liver tissue. We acknowledge Dr. Ryszard Kole for helpful insights on alternate splicing. Fibroblast cell lines were purchased from the American Type Tissue Culture Facility (Rockville, MD). This research was funded by the National Institutes of Health (R29HL52663).
PY - 1997
Y1 - 1997
N2 - Lecithin:cholesterol acyltransferase (LCAT), an important enzyme affecting reverse cholesterol transport, is expressed in liver and cultured fibroblasts. Sequencing of LCAT cDNA clones demonstrated the coexistence of two mRNA products. In addition to the normal transcript, we identified an alternate message with a splice-mediated insertion of a 95 bp Alu cassette at the junction of exons 5 and 6. In humans, the alternate transcript represents 5-20% of the complete LCAT message in cultured fibroblasts and liver. It is present in humans and the great apes but not in lesser apes (gibbon, siamang) or lower-order primates (e.g., old or new world monkeys). Sequencing of intron 5 of the LCAT locus in several primates revealed a G→A transition at the splice donor recognition site in the Alu repeat of the gibbon and a G→A substitution in the last position of the 95 bp Alu sequence of the rhesus monkey, an old world monkey. Both substitutions have been associated with exon skipping in other genes. These results demonstrate that alternative splicing of LCAT mRNA is variant among primates and suggest a potential role of Alu elements in the evolutionary diversity of proteins.
AB - Lecithin:cholesterol acyltransferase (LCAT), an important enzyme affecting reverse cholesterol transport, is expressed in liver and cultured fibroblasts. Sequencing of LCAT cDNA clones demonstrated the coexistence of two mRNA products. In addition to the normal transcript, we identified an alternate message with a splice-mediated insertion of a 95 bp Alu cassette at the junction of exons 5 and 6. In humans, the alternate transcript represents 5-20% of the complete LCAT message in cultured fibroblasts and liver. It is present in humans and the great apes but not in lesser apes (gibbon, siamang) or lower-order primates (e.g., old or new world monkeys). Sequencing of intron 5 of the LCAT locus in several primates revealed a G→A transition at the splice donor recognition site in the Alu repeat of the gibbon and a G→A substitution in the last position of the 95 bp Alu sequence of the rhesus monkey, an old world monkey. Both substitutions have been associated with exon skipping in other genes. These results demonstrate that alternative splicing of LCAT mRNA is variant among primates and suggest a potential role of Alu elements in the evolutionary diversity of proteins.
KW - Alu sequence
KW - LCAT
KW - Molecular evolution
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U2 - 10.1016/S0378-1119(97)00022-X
DO - 10.1016/S0378-1119(97)00022-X
M3 - Article
C2 - 9197549
AN - SCOPUS:0030979527
SN - 0378-1119
VL - 190
SP - 309
EP - 313
JO - Gene
JF - Gene
IS - 2
ER -