RRC ID 31781
Author Okada M, Nakajima K, Yaoita Y.
Title Translational regulation by the 5'-UTR of thyroid hormone receptor α mRNA.
Journal J Biochem
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.
Volume 151(5)
Pages 519-31
Published 2012-5-1
DOI 10.1093/jb/mvs026
PII mvs026
PMID 22406405
MeSH 5' Untranslated Regions / genetics* Amino Acid Sequence Animals Anura / genetics Cell Line Humans Molecular Sequence Data Polymerase Chain Reaction RNA, Messenger / genetics* Thyroid Hormone Receptors alpha / genetics* Transcription, Genetic / genetics* Urodela / genetics
IF 2.476
Times Cited 10
Xenopus tropicalis Nigerian H line Ivory Coast line