Glucocorticoid regulation of human pulmonary surfactant protein-B mRNA stability involves the 3'-untranslated region.
Glucocorticoid regulation of human pulmonary surfactant protein-B mRNA stability involves the 3'-untranslated region.
复制标题
糖皮质激素对人肺表面活性蛋白-B mRNA 稳定性的调节涉及 3-非翻译区。
DOI：
10.1165/rcmb.2007-0303oc
复制
发表时间：
2008
影响因子：
6.4
通讯作者：
Alcorn,JosephL
中科院分区：
文献类型：
--
作者：
Huang,HelenW;Bi,Weizhen;Jenkins,GayeN;Alcorn,JosephL
Expression of pulmonary surfactant, a complex mixture of lipids and proteins that acts to reduce alveolar surface tension, is developmentally regulated and restricted to lung alveolar type II cells. The hydrophobic protein surfactant protein-B (SP-B) is essential in surfactant function, and insufficient levels of SP-B result in severe respiratory dysfunction. Glucocorticoids accelerate fetal lung maturity and surfactant synthesis both experimentally and clinically. Glucocorticoids act transcriptionally and post-transcriptionally to increase steady-state levels of human SP-B mRNA; however, the mechanism(s) by which glucocorticoids act post-transcriptionally is unknown. We hypothesized that glucocorticoids act post-transcriptionally to increase SP-B mRNA stability via sequence-specific mRNA–protein interactions. We found that glucocorticoids increase SP-B mRNA stability in isolated human type II cells and in nonpulmonary cells, but do not alter mouse SP-B mRNA stability in a mouse type II cell line. Deletion analysis of an artificially-expressed SP-B mRNA indicates that the SP-B mRNA 3′-untranslated region (UTR) is necessary for stabilization, and the region involved can be restricted to a 126-nucleotide-long region near the SP-B coding sequence. RNA electrophoretic mobility shift assays indicate that cytosolic proteins bind to this region in the absence or presence of glucocorticoids. The formation of mRNA:protein complexes is not seen in other regions of the SP-B mRNA 3′-UTR. These results indicate that a specific 126-nucleotide region of human SP-B 3′-UTR is necessary for increased SP-B mRNA stability by glucocorticoids by a mechanism that is not lung cell specific and may involve mRNA–protein interactions.
