Alternative splicing in lecithin:cholesterol acyltransferase mRNA: An evolutionary paradigm in humans and great apes

Michael Miller, Karen Zeller

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)309-313
Number of pages5
JournalGene
Volume190
Issue number2
DOIs
StatePublished - Jun 7 1997

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Keywords

  • Alu sequence
  • LCAT
  • Molecular evolution

ASJC Scopus subject areas

  • Genetics

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