Glucocorticoid-mediated destabilization of cyclin D3 mRNA involves RNA-protein interactions in the 3'-untranslated region of the mRNA

Eduardo A. Garcia-Gras, Ping Chi, E Aubrey Thompson

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Glucocorticoids regulate the expression of the G 1 progression factor, cyclin D3. Cyclin D3 messenger RNA (CcnD3 mRNA) stability decreases rapidly when murine T lymphoma cells are treated with the synthetic glucocorticoid dexamethasone. Basal stability of CcnD3 mRNA is regulated by sequences within the 3'-untranslated region (3'-UTR). RNA-protein interactions occurring within the CcnD3 3'-UTR have been analyzed by RNA electrophoretic mobility shift assay. Three sites of RNA-protein interaction have been mapped using this approach. These elements include three pyrimidine-rich domains of 25, 26, and 37 nucleotides. When the cyclin D3 3'-UTR was stably overexpressed, the endogenous CcnD3 mRNA was no longer regulated by dexamethasone. Likewise, overexpression of a 215-nucleotide transgene that contains the 26- and 37-nucleotide elements blocks glucocorticoid inhibition of CcnD3 mRNA expression. These observations suggest that the 215-nucleotide 3'-UTR element may act as a molecular decoy, competing for proteins that bind to the endogenous transcript and thereby attenuating glucocorticoid responsiveness. UV-cross-linking experiments showed that two proteins of approximate molecular weight 37,000 and 52,000 bind to this 3'-UTR element.

Original languageEnglish (US)
Pages (from-to)22001-22008
Number of pages8
JournalJournal of Biological Chemistry
Volume275
Issue number29
StatePublished - Jul 21 2000
Externally publishedYes

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Cyclin D3
3' Untranslated Regions
Glucocorticoids
RNA
Messenger RNA
Nucleotides
Proteins
Dexamethasone
Electrophoretic mobility
T-Cell Lymphoma
RNA Stability
Electrophoretic Mobility Shift Assay
Transgenes
Assays
Molecular Weight
Molecular weight

ASJC Scopus subject areas

  • Biochemistry

Cite this

Glucocorticoid-mediated destabilization of cyclin D3 mRNA involves RNA-protein interactions in the 3'-untranslated region of the mRNA. / Garcia-Gras, Eduardo A.; Chi, Ping; Thompson, E Aubrey.

In: Journal of Biological Chemistry, Vol. 275, No. 29, 21.07.2000, p. 22001-22008.

Research output: Contribution to journalArticle

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