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A primate-specific RNA-binding protein (RBMXL3) is involved in glucocorticoid regulation of human pulmonary surfactant protein B (SP-B) mRNA stability
- Source :
- Am J Physiol Lung Cell Mol Physiol
- Publication Year :
- 2021
- Publisher :
- American Physiological Society, 2021.
-
Abstract
- The ability of pulmonary surfactant to reduce alveolar surface tension requires adequate levels of surfactant protein B (SP-B). Dexamethasone (DEX) increases human SP-B expression, in part, through increased SP-B mRNA stability. A 30-nt-long hairpin element (RBE) in the 3′-untranslated region of human SP-B mRNA mediates both DEX-induced and intrinsic mRNA stabilities, but the mechanism is unknown. Proteomic analysis of RBE-interacting proteins identified a primate-specific protein, RNA-binding motif X-linked-like-3 (RBMXL3). siRNA directed against RBMXL3 reduces DEX-induced SP-B mRNA expression in human bronchoalveolar cells. Human SP-B mRNA stability, measured by our dual cistronic plasmid assay, is unaffected by DEX in mouse lung epithelial cells lacking RBMXL3, but DEX increases human SP-B mRNA stability when RBMXL3 is expressed and requires the RBE. In the absence of DEX, RBE interacts with cellular proteins, reducing intrinsic SP-B mRNA stability in human and mouse lung epithelial cells. RBMXL3 specifically binds the RBE in vitro, whereas RNA immunoprecipitation and affinity chromatography analyses indicate that binding is enhanced in the presence of DEX. These results describe a model where intrinsic stability of human SP-B mRNA is reduced through binding of cellular mRNA decay factors to RBE, which is then relieved through DEX-enhanced binding of primate-specific RBMXL3.
- Subjects :
- 0301 basic medicine
Pulmonary and Respiratory Medicine
Pulmonary Surfactant-Associated Proteins
Physiology
RNA Stability
RNA-binding protein
Dexamethasone
03 medical and health sciences
Mice
0302 clinical medicine
Pulmonary surfactant
Physiology (medical)
medicine
Animals
Humans
RNA, Messenger
Protein Precursors
Glucocorticoids
Messenger RNA
Chemistry
Retroposon
RNA-Binding Proteins
Cell Biology
Surfactant protein B
Cell biology
Primate specific
030104 developmental biology
HEK293 Cells
A549 Cells
Glucocorticoid
hormones, hormone substitutes, and hormone antagonists
030215 immunology
medicine.drug
Research Article
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Am J Physiol Lung Cell Mol Physiol
- Accession number :
- edsair.doi.dedup.....6dd43817982423aa9d3705e834db5e2a