Inhibitory activity of the human papillomavirus type 1 AU-rich element correlates inversely with the levels of the elav-like HuR protein in the cell cytoplasm

Abstract

We have analysed the activity of the negative element in the late 3' untranslated region of the cutaneous human papillomavirus type 1 (HPV-1) mRNAs in a panel of epithelial cells, of both mucosal and cutaneous origin. The inhibitory activity was cell line dependent. Determination of the levels of heterogeneous ribonucleoprotein C1/C2 and HuR that have been shown previously to interact specifically with the HPV-1 negative RNA element revealed that low levels of the HuR protein in the cytoplasmic fraction correlated with high inhibitory activity of the HPV-1 element, whereas cell lines displaying low inhibitory activity contained high levels of HuR in the cytoplasm. These results suggested that the HuR protein has a positive effect on HPV-1 late gene expression.

HuR and mRNA stability

“…Gorospe and colleagues have also correlated the increased cytoplasmic localization of HuR during late G1, S and G2 phases in colorectal carcinoma RKO cells with the stabilization of ARE-containing mRNA [82]. Similarly, an increased ability of epithelial cells containing relatively high amounts of cytoplasmic HuR to stabilize mRNA containing the human papillomavirus type 1 AU-rich element has been reported [117]. These data are consistent with the increased cytoplasmic localization of HuR following heat shock [85], a stress known to stabilize ARE-containing mRNA [74].…”

Terminal Adenosyl Transferase Activity of Posttranscriptional Regulator HuR Revealed by Confocal On-Bead Screening

“…1,2 Recently, evidence has been accumulating that dysregulated expression and activity of the mRNA binding protein HuR (Hu protein R), a key ARE pathway node, may be fundamentally linked to the development, progression, and prognosis of malignant diseases. [3][4][5][6][7][8][9][10][11][12][13][14] Consequently, there is increasing interest in HuR as a drug target in the recent literature. 4,15,16 Nevertheless, there is still no HuRtargeted drug in pharmaceutical drug development to the best of our knowledge.…”

The effect of RNA secondary structures on RNA-ligand binding and the modifier RNA mechanism: a quantitative model

“…Most of these control mechanisms involve specific RNA-protein interactions that depend crucially on the recognition of sequence and/or structural features of the RNA [28]. Examples include the regulation of viral life-cycles [6,9,42,60], pre-mRNA processing [39], nuclear RNA export [15], and the control of RNA degradation [7] and stabilization [47].…”