The mRNA structure has potent regulatory effects on type 2 iodothyronine deiodinase expression

B. Gereben, Anna Kollár, John W. Harney, P. ReedLarsen

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

Type 2 deiodinase (D2) is a selenoenzyme catalyzing the activation of T4 to T3. D2 activity/mRNA ratios are often low, suggesting that there is significant posttranscriptional regulation. The D2 mRNA in higher vertebrates is more than 6 kb, containing long 5′ and 3′ untranslated regions (UTRs). The D2 5′UTRs are greater than 600 nucleotides and contain 3-5 short open reading frames. These full-length 5′UTRs reduce the D2 translation efficiency approximately 5-fold. The inhibition by human D2 5′UTR is localized to a region containing the first short open reading frame encoding a tripeptide - MKG. This inhibition was abolished by mutating the AUG start codon and weakened by modification of the essential purine of the Kozak consensus. Deletion of the 3.7-kb 3′UTR of the chicken D2 mRNA increased D2 activity approximately 3.8-fold due to an increase in D2 mRNA half-life. In addition, alternatively spliced D2 mRNA transcripts similar in size to the major 6- to 7-kb D2 mRNAs but not encoding an active enzyme are present in both human and chicken tissues. Our results indicate that a number of factors reduce the D2 protein levels. These mechanisms, together with the short half-life of the protein, ensure limited expression of this key regulator of T4 activation.

Original languageEnglish
Pages (from-to)1667-1679
Number of pages13
JournalMolecular Endocrinology
Volume16
Issue number7
DOIs
Publication statusPublished - Jan 1 2002

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology

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