Differential translation of TOP mRNAs in rapamycin-treated human B lymphocytes

• Published in: Biochimica et biophysica acta 2003-07, Vol.1628 (1), p.50-55
• Main Authors: Zhu, Jianfeng, Spencer, Eliott D, Kaspar, Roger L
• Format: Article
• Language: English
• Subjects: 5' Untranslated Regions; 5′ UTR; B-Lymphocytes - drug effects; B-Lymphocytes - metabolism; Base Sequence; Cytidine - metabolism; Gene Expression Regulation; Genes, Reporter; Heterogeneous-Nuclear Ribonucleoproteins - metabolism; Humans; Immunosuppressive Agents - pharmacology; Molecular Sequence Data; Mutation; Plasmids - metabolism; Polyribosomes - metabolism; Protein Biosynthesis - drug effects; Rapamycin; Ribosomal Proteins - metabolism; Ribosomes - metabolism; RNA, Messenger - metabolism; Sirolimus - pharmacology; TOP mRNA; Transfection; Translational regulation
• ISSN: 0167-4781; 0006-3002; 1879-2634
• DOI: 10.1016/S0167-4781(03)00117-9

TOP mRNAs (contain a 5′ terminal oligo pyrimidine tract) are differentially translated in rapamycin-treated human B lymphocytes. Following rapamycin treatment, ribosomal protein (rp) and translation elongation factor TOP mRNAs were translationally repressed, whereas hnRNP A1 TOP mRNA was not. Poly(A)-binding protein (Pabp1) TOP mRNA was translationally repressed under all conditions tested. To investigate the mechanism involved, chimeric mRNAs containing the hnRNP A1 5′ untranslated region (UTR) linked to the human growth hormone (hGH) reporter were analyzed. Wild-type hnRNP A1 construct mRNA behaved similarly to endogenous hnRNP A1, whereas a single mutation (guanosine to cytidine) within the TOP element resulted in increased translational regulation. These results suggest that TOP mRNA translation can be modulated and that all TOP mRNAs are not translated with equal efficiency.