Characterization of the 5′-flanking and 5′-untranslated regions of the cyclic adenosine 3′,5′-monophosphate-responsive human type 2 iodothyronine deiodinase gene

T. Bartha, Sung Woo Kim, Domenico Salvatore, B. Gereben, Helen M. Tu, John W. Harney, P. Rudas, P. Reed Larsen

Research output: Contribution to journalArticle

Abstract

The type 2 iodothyronine deiodinase (D2) catalyzes T4 activation. In humans, unlike rodents, it is widely expressed, and its action probably contributes to both intracellular and plasma T3 pools. We have isolated the 6.5-kb 5′-flanking region (FR) and the previously uncloned 553 nucleotides (nt) of the 5′-untranslated region (UTR) of hdio2. The 5′-UTR is complex, with three transcription start sites (TSS) (708, 31, and ∼24 nt 5′ to the ATG), an alternatively spliced approximately 300-nt intron in the 5′-UTR, and three short open reading frames 5′ to the initiator ATG. The previously reported approximately 7.5-kb D2 messenger RNA (mRNA) is actually an approximately 7-kb doublet that is present in thyroid, pituitary, cardiac and skeletal muscle, and possibly brain, but with only the longer transcript in placenta. A canonical cAMP response element-binding protein-binding site is present at about 90 bp 5′ to the most 5′-TSS. It accounts for the robust response of the 6.8-kb hdio2 5′-FR to protein kinase A. Forskolin increases D2 mRNA in human thyroid cells, which may explain the high D2 mRNA in Graves' thyroid and thyroid adenomas. The hdio2 gene structure and Northern blot results suggest that D2 expression is tightly controlled and tissue specific.

Original languageEnglish
Pages (from-to)229-237
Number of pages9
JournalEndocrinology
Volume141
Issue number1
DOIs
Publication statusPublished - 2000

Fingerprint

Iodide Peroxidase
5' Untranslated Regions
Adenosine
Thyroid Gland
Nucleotides
5' Flanking Region
Transcription Initiation Site
Messenger RNA
Genes
Cyclic AMP Response Element-Binding Protein
Colforsin
Cyclic AMP-Dependent Protein Kinases
Thyroid Neoplasms
Protein Binding
Northern Blotting
Introns
Placenta
Open Reading Frames
Rodentia
Myocardium

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Characterization of the 5′-flanking and 5′-untranslated regions of the cyclic adenosine 3′,5′-monophosphate-responsive human type 2 iodothyronine deiodinase gene. / Bartha, T.; Kim, Sung Woo; Salvatore, Domenico; Gereben, B.; Tu, Helen M.; Harney, John W.; Rudas, P.; Reed Larsen, P.

In: Endocrinology, Vol. 141, No. 1, 2000, p. 229-237.

Research output: Contribution to journalArticle

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