Translational regulation by steroids. Identification of a steroid modulatory element in the 5'-untranslated region of the myelin basic protein messenger RNA.
Although steroids have been implicated in post-transcriptional regulation, their effects on mRNA translation rates have been uncertain. We have used a cell-free translation system programmed with synthetic messages to show that steroids can alter the translation rates of a number of myelin protein mRNAs and the mRNA encoding a non-myelin protein, the estrogen receptor. Through the use of deletion analysis, site-directed mutagenesis, and chimeric mRNAs we have identified a 9-nucleotide segment in the 5'-untranslated region of one myelin protein mRNA that is necessary for steroid action. Steroid-mediated translational regulation is discussed in terms of myelination where subtle developmental changes in protein composition of the membrane have significant consequences on its morphology and function. We propose that the modulation of mRNA translation rates by steroids is a more general phenomenon that may serve as another mechanism by which steroids can regulate gene expression.
Verdi
J M
JM
Mental Retardation Research Center, UCLA School of Medicine 90024.
Campagnoni
A T
AT
D000818:Animals; D001483:Base Sequence; D002474:Cell-Free System; D003001:Cloning, Molecular; D004958:Estradiol / Q000494:pharmacology*; D006854:Hydrocortisone / Q000494:pharmacology*; D007700:Kinetics; D008715:Methionine / Q000378:metabolism; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D004676:Myelin Basic Protein / Q000096:biosynthesis / Q000235:genetics*; D015345:Oligonucleotide Probes; D016133:Polymerase Chain Reaction; D014176:Protein Biosynthesis / Q000187:drug effects*; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics*; D011817:Rabbits; D015183:Restriction Mapping; D012156:Reticulocytes / Q000378:metabolism; D014158:Transcription, Genetic; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics
D004676:Myelin Basic Protein; D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D004958:Estradiol; D008715:Methionine; D014446:Tyrosine 3-Monooxygenase; D006854:Hydrocortisone