title: Translational regulation by the 5'-UTR of thyroid hormone receptor α mRNA.
abstract: Thyroid hormone (TH) regulates gene transcription by binding to the thyroid hormone receptor (TR) and plays a critical role in the regulation of development, growth and metabolism. The ligated TR activates many effector genes, which contributes to the orchestrated remodelling of the amphibian metamorphosis. However, the mechanisms regulating TRα protein level remain unknown. We determined the nucleotide sequences of the 5'-untranslated regions (5'-UTRs) in amphibian TRα mRNAs. The TRα 5'-UTR contains evolutionarily conserved regions. We demonstrated that a 161-nt stretch of the Xenopus TRα 5'-UTR strongly represses the translation of the downstream open reading frame in both frog and human cell lines, as well as in a cell-free translation system. An analysis using successive deletions of the TRα 5'-UTR revealed five elements possessing translational repressive activity. We analysed two elements, the 14-nt GC-rich region and the 15-nt upstream open reading frame (uORF), by introducing point mutations. This analysis showed that the GC-rich region, which shares its nucleotide sequence with the Sp1-binding site, requires stringent sequence specificity at a nucleotide level for translational repression to take place, whereas under our study conditions, the uORF does not. This study provides an example of complex translational regulation by multiple elements.
authors.affiliation: Division of Embryology and Genetics, Institute for Amphibian Biology, Graduate School of Science, Hiroshima University, Higashihiroshima 739-8526, Japan.
authors.forename: Morihiro
authors.initials: M
authors.lastname: Okada
authors.forename: Keisuke
authors.initials: K
authors.lastname: Nakajima
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Yaoita
mesh_terms: D020121:5' Untranslated Regions / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D001001:Anura / Q000235:genetics; D002460:Cell Line; D006801:Humans; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics*; D037021:Thyroid Hormone Receptors alpha / Q000235:genetics*; D014158:Transcription, Genetic / Q000235:genetics*; D014562:Caudata / Q000235:genetics
chemical_list: D020121:5' Untranslated Regions; D012333:RNA, Messenger; D037021:Thyroid Hormone Receptors alpha