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Human catechol-O-methyltransferase haplotypes modulate protein expression by altering mRNA secondary structure.

Publication ,  Journal Article
Nackley, AG; Shabalina, SA; Tchivileva, IE; Satterfield, K; Korchynskyi, O; Makarov, SS; Maixner, W; Diatchenko, L
Published in: Science
December 22, 2006

Catechol-O-methyltransferase (COMT) is a key regulator of pain perception, cognitive function, and affective mood. Three common haplotypes of the human COMT gene, divergent in two synonymous and one nonsynonymous position, code for differences in COMT enzymatic activity and are associated with pain sensitivity. Haplotypes divergent in synonymous changes exhibited the largest difference in COMT enzymatic activity, due to a reduced amount of translated protein. The major COMT haplotypes varied with respect to messenger RNA local stem-loop structures, such that the most stable structure was associated with the lowest protein levels and enzymatic activity. Site-directed mutagenesis that eliminated the stable structure restored the amount of translated protein. These data highlight the functional significance of synonymous variations and suggest the importance of haplotypes over single-nucleotide polymorphisms for analysis of genetic variations.

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Published In

Science

DOI

EISSN

1095-9203

Publication Date

December 22, 2006

Volume

314

Issue

5807

Start / End Page

1930 / 1933

Location

United States

Related Subject Headings

  • Transfection
  • Rats
  • RNA, Messenger
  • RNA Stability
  • Polymorphism, Single Nucleotide
  • Phenotype
  • Pain
  • PC12 Cells
  • Nucleic Acid Conformation
  • Mutagenesis, Site-Directed
 

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Nackley, A. G., Shabalina, S. A., Tchivileva, I. E., Satterfield, K., Korchynskyi, O., Makarov, S. S., … Diatchenko, L. (2006). Human catechol-O-methyltransferase haplotypes modulate protein expression by altering mRNA secondary structure. Science, 314(5807), 1930–1933. https://doi.org/10.1126/science.1131262
Nackley, A. G., S. A. Shabalina, I. E. Tchivileva, K. Satterfield, O. Korchynskyi, S. S. Makarov, W. Maixner, and L. Diatchenko. “Human catechol-O-methyltransferase haplotypes modulate protein expression by altering mRNA secondary structure.Science 314, no. 5807 (December 22, 2006): 1930–33. https://doi.org/10.1126/science.1131262.
Nackley AG, Shabalina SA, Tchivileva IE, Satterfield K, Korchynskyi O, Makarov SS, et al. Human catechol-O-methyltransferase haplotypes modulate protein expression by altering mRNA secondary structure. Science. 2006 Dec 22;314(5807):1930–3.
Nackley, A. G., et al. “Human catechol-O-methyltransferase haplotypes modulate protein expression by altering mRNA secondary structure.Science, vol. 314, no. 5807, Dec. 2006, pp. 1930–33. Pubmed, doi:10.1126/science.1131262.
Nackley AG, Shabalina SA, Tchivileva IE, Satterfield K, Korchynskyi O, Makarov SS, Maixner W, Diatchenko L. Human catechol-O-methyltransferase haplotypes modulate protein expression by altering mRNA secondary structure. Science. 2006 Dec 22;314(5807):1930–1933.
Journal cover image

Published In

Science

DOI

EISSN

1095-9203

Publication Date

December 22, 2006

Volume

314

Issue

5807

Start / End Page

1930 / 1933

Location

United States

Related Subject Headings

  • Transfection
  • Rats
  • RNA, Messenger
  • RNA Stability
  • Polymorphism, Single Nucleotide
  • Phenotype
  • Pain
  • PC12 Cells
  • Nucleic Acid Conformation
  • Mutagenesis, Site-Directed