Dual posttranscriptional targets of retinoic acid-induced gene expression

• Published in: Journal of cellular biochemistry Vol. 72; no. 3; pp. 411 - 422
• Main Authors: Manji, Shehnaaz S., Pearson, Richard B., Pardee, Marshall, Paspaliaris, Vasilias, d'Apice, Anthony, Martin, T. John, Ng, Kong Wah
• Format: Journal Article
• Language: English
• Published: New York John Wiley & Sons, Inc 01.03.1999
• Subjects: Alkaline Phosphatase - genetics; alkaline phosphatase gene regulation; Animals; Blotting, Western; Cell Nucleus - chemistry; Cells, Cultured; Cytoplasm - chemistry; differentiation; Gene Expression Regulation; Lymphotoxin-alpha - physiology; Nuclear Proteins - physiology; Phosphoamino Acids - physiology; Phosphopeptides - physiology; Phosphorylation; posttranscriptional nuclear processing; Precipitin Tests; Rats; Reverse Transcriptase Polymerase Chain Reaction; Ribonucleoprotein, U1 Small Nuclear - blood; Ribonucleoprotein, U1 Small Nuclear - drug effects; Ribonucleoprotein, U1 Small Nuclear - physiology; RNA-Binding Proteins; Serine-Arginine Splicing Factors; Spliceosomes - physiology; splicing; SR proteins; TGF-β; Time Factors; TNF-α; Tretinoin - physiology; Tumor Necrosis Factor-alpha - physiology; U1 snRNP
• ISSN: 0730-2312; 1097-4644
• DOI: 10.1002/(SICI)1097-4644(19990301)72:3<411::AID-JCB10>3.0.CO;2-X

Retinoic acid‐induced differentiation of the pre‐osteoblastic cell line, UMR 201, is associated with a marked increase in the proficiency of posttranscriptional nuclear processing of alkaline phosphatase mRNA. In this study we attempted to correlate the posttranscriptional actions of retinoic acid with changes in phosphorylation, or abundance of spliceosome components, or both. Treatment with retinoic acid for periods of ≤4 h resulted in dephosphorylation of nuclear U1 70K protein without affecting its abundance. Peptide mapping showed that U1 70K dephosphorylation was related to the disappearance of one specific phosphopeptide out of four major U1 70K phosphopeptides. A twofold decrease in mRNA expression of an isoform of alternative splicing factor that inhibits splicing was also observed over the same period. Tumor necrosis factor‐α, which enhances the posttranscriptional action of retinoic acid, reduced U170K mRNA expression, while an inhibition of retinoic acid action by transforming growth factor‐β was associated with a marked increase in U1 70K mRNA levels. Our results draw attention to the complex interactions between short‐ and long‐term alterations in the abundance and functional status of U1 70K, as well as SR proteins by growth and/or differentiation factors in the regulation of spliceosome formation and function. J. Cell. Biochem. 72:411–422, 1999. © 1999 Wiley‐Liss, Inc.