Estrogen Regulation of Messenger RNA Stability
Abstract
Estrogen administration to male Xenopus laevis results in the inhibition of serum albumin gene expression through the destabilization of albumin mRNA. This process occurs during the massive induction and stabilization of vitellogenin mRNA in the liver, and is mediated through an estrogen receptor-dependent process. This dissertation examines: 1) potential estrogen-induced changes in albumin mRNA primary sequence leading to its destabilization; 2) the possibility that other serum protein-coding mRNAs are coordinately regulated by estrogen; 3) the effect of metabolic inhibitors on the decay process; 4) the intracellular localization of the degradation; and 5) RNA degradation through the development of an in vitro assay system. Estrogen does not modify the primary sequence of albumin mRNA in regulating its stability. This conclusion was based on comparison of albumin cDNA sequences determined from libraries prepared from RNA isolated from control versus estrogen-treated animals. Since the albumin cDNA sequences were identical, unique secondary structures caused by estrogen-treatment could not be responsible for targeting albumin degradation. To investigate whether other serum proteins were similarly regulated by estrogen, several serum protein cDNAs were tested for coordinate posttranscriptional regulation of their cognate mRNAs, and their primary and secondary structures were analyzed. From this study it was determined that estrogen also destabilized mRNAs encoding 7-fibrinogen, transferrin, clone 12B, and the second protein of inter-a-trypsin inhibitor. Messenger RNAlevels for these serum protein-coding mRNAs decrease to low levels in the cytoplasm in response to estrogen with little effects on steady-state RNA levels in the nucleus. Ferritin mRNA (encoding an intracellular protein) levels were unaffected upon estrogen-treatment.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 17, 1990
- Accession Number
- AD1010973
Entities
People
- John E. Moskaitis
Organizations
- Uniformed Services University of the Health Sciences