The mRNA structure has potent regulatory effects on type 2 iodothyronine deiodinase expression.
Type 2 deiodinase (D2) is a selenoenzyme catalyzing the activation of T(4) to T(3). 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 T(4) activation.
Gereben
Balázs
B
Institute of Experimental Medicine, Department of Neurobiology, Budapest H-1083, Hungary.
Kollár
Anna
A
Harney
John W
JW
Larsen
P Reed
PR
D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D002645:Chickens / Q000235:genetics; D003001:Cloning, Molecular; D018387:Codon, Initiator; D004251:DNA Transposable Elements; D015971:Gene Expression Regulation, Enzymologic; D006207:Half-Life; D006801:Humans; D007453:Iodide Peroxidase / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D009690:Nucleic Acid Conformation; D014176:Protein Biosynthesis; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000737:chemistry* / Q000378:metabolism; D000097564:Iodothyronine Deiodinase Type II
D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D018387:Codon, Initiator; D004251:DNA Transposable Elements; D007453:Iodide Peroxidase; D012333:RNA, Messenger; D000097564:Iodothyronine Deiodinase Type II