Optional exon in the 5'-untranslated region of 3-hydroxy-3-methylglutaryl coenzyme A synthase gene

Conserved sequence and splicing pattern in humans and hamsters

G. Gil, J. R. Smith, J. L. Goldstein, M. S. Brown

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

3-Hydroxy-3-methylglutaryl coenzyme A synthase (hydroxymethylglutaryl-CoA synthase, EC 4.1.3.5) is a negatively regulated enzyme in the synthetic pathway for cholesterol, isopentenyl tRNA, and other isoprenoids. The 5'-untranslated region of the mRNA for Chinese hamster hydroxymethylglutaryl-CoA synthase contains an optional exon of 59 nucleotides located 10 nucleotides upstream of the translation start site. About 50% of the mRNAs contain this exon, and the other 50% lack it owing to differential intron splicing. We show that the two transcripts are found in similar ratios in multiple tissues of the Syrian hamster, including the brain. The relative amounts of the two transcripts in brain and liver are constant from day 0 to day 75 of life. A similar alternative splicing pattern for hydroxymethylgutaryl-CoA synthase was observed in three human tissues: cultured fibroblasts, fetal adrenal gland, and fetal liver. A cDNA for human synthase had 90% homology to the hamster sequence in the region corresponding to the optional exon. This sequence contains a 20 out of 26 nucleotide match with the sequence immediately upstream of the initiator AUG codon in the mRNA for hamster hydroxymethylglutaryl-CoA reductase, the enzyme that follows the synthase in the isoprenoid biosynthetic pathway. These findings raise the possibility that the optional exon plays an important, conserved functional role in humans and hamsters.

Original languageEnglish (US)
Pages (from-to)1863-1866
Number of pages4
JournalProceedings of the National Academy of Sciences of the United States of America
Volume84
Issue number7
StatePublished - 1987

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Hydroxymethylglutaryl-CoA Synthase
Conserved Sequence
5' Untranslated Regions
Cricetinae
Exons
Nucleotides
Terpenes
Messenger RNA
Genes
Hydroxymethylglutaryl CoA Reductases
Initiator Codon
Liver
Biosynthetic Pathways
Mesocricetus
Brain
Alternative Splicing
Enzymes
Coenzyme A
Adrenal Glands
Transfer RNA

ASJC Scopus subject areas

  • General
  • Genetics

Cite this

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title = "Optional exon in the 5'-untranslated region of 3-hydroxy-3-methylglutaryl coenzyme A synthase gene: Conserved sequence and splicing pattern in humans and hamsters",
abstract = "3-Hydroxy-3-methylglutaryl coenzyme A synthase (hydroxymethylglutaryl-CoA synthase, EC 4.1.3.5) is a negatively regulated enzyme in the synthetic pathway for cholesterol, isopentenyl tRNA, and other isoprenoids. The 5'-untranslated region of the mRNA for Chinese hamster hydroxymethylglutaryl-CoA synthase contains an optional exon of 59 nucleotides located 10 nucleotides upstream of the translation start site. About 50{\%} of the mRNAs contain this exon, and the other 50{\%} lack it owing to differential intron splicing. We show that the two transcripts are found in similar ratios in multiple tissues of the Syrian hamster, including the brain. The relative amounts of the two transcripts in brain and liver are constant from day 0 to day 75 of life. A similar alternative splicing pattern for hydroxymethylgutaryl-CoA synthase was observed in three human tissues: cultured fibroblasts, fetal adrenal gland, and fetal liver. A cDNA for human synthase had 90{\%} homology to the hamster sequence in the region corresponding to the optional exon. This sequence contains a 20 out of 26 nucleotide match with the sequence immediately upstream of the initiator AUG codon in the mRNA for hamster hydroxymethylglutaryl-CoA reductase, the enzyme that follows the synthase in the isoprenoid biosynthetic pathway. These findings raise the possibility that the optional exon plays an important, conserved functional role in humans and hamsters.",
author = "G. Gil and Smith, {J. R.} and Goldstein, {J. L.} and Brown, {M. S.}",
year = "1987",
language = "English (US)",
volume = "84",
pages = "1863--1866",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
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TY - JOUR

T1 - Optional exon in the 5'-untranslated region of 3-hydroxy-3-methylglutaryl coenzyme A synthase gene

T2 - Conserved sequence and splicing pattern in humans and hamsters

AU - Gil, G.

AU - Smith, J. R.

AU - Goldstein, J. L.

AU - Brown, M. S.

PY - 1987

Y1 - 1987

N2 - 3-Hydroxy-3-methylglutaryl coenzyme A synthase (hydroxymethylglutaryl-CoA synthase, EC 4.1.3.5) is a negatively regulated enzyme in the synthetic pathway for cholesterol, isopentenyl tRNA, and other isoprenoids. The 5'-untranslated region of the mRNA for Chinese hamster hydroxymethylglutaryl-CoA synthase contains an optional exon of 59 nucleotides located 10 nucleotides upstream of the translation start site. About 50% of the mRNAs contain this exon, and the other 50% lack it owing to differential intron splicing. We show that the two transcripts are found in similar ratios in multiple tissues of the Syrian hamster, including the brain. The relative amounts of the two transcripts in brain and liver are constant from day 0 to day 75 of life. A similar alternative splicing pattern for hydroxymethylgutaryl-CoA synthase was observed in three human tissues: cultured fibroblasts, fetal adrenal gland, and fetal liver. A cDNA for human synthase had 90% homology to the hamster sequence in the region corresponding to the optional exon. This sequence contains a 20 out of 26 nucleotide match with the sequence immediately upstream of the initiator AUG codon in the mRNA for hamster hydroxymethylglutaryl-CoA reductase, the enzyme that follows the synthase in the isoprenoid biosynthetic pathway. These findings raise the possibility that the optional exon plays an important, conserved functional role in humans and hamsters.

AB - 3-Hydroxy-3-methylglutaryl coenzyme A synthase (hydroxymethylglutaryl-CoA synthase, EC 4.1.3.5) is a negatively regulated enzyme in the synthetic pathway for cholesterol, isopentenyl tRNA, and other isoprenoids. The 5'-untranslated region of the mRNA for Chinese hamster hydroxymethylglutaryl-CoA synthase contains an optional exon of 59 nucleotides located 10 nucleotides upstream of the translation start site. About 50% of the mRNAs contain this exon, and the other 50% lack it owing to differential intron splicing. We show that the two transcripts are found in similar ratios in multiple tissues of the Syrian hamster, including the brain. The relative amounts of the two transcripts in brain and liver are constant from day 0 to day 75 of life. A similar alternative splicing pattern for hydroxymethylgutaryl-CoA synthase was observed in three human tissues: cultured fibroblasts, fetal adrenal gland, and fetal liver. A cDNA for human synthase had 90% homology to the hamster sequence in the region corresponding to the optional exon. This sequence contains a 20 out of 26 nucleotide match with the sequence immediately upstream of the initiator AUG codon in the mRNA for hamster hydroxymethylglutaryl-CoA reductase, the enzyme that follows the synthase in the isoprenoid biosynthetic pathway. These findings raise the possibility that the optional exon plays an important, conserved functional role in humans and hamsters.

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