Abstract
Recently, we have cloned and characterized a coactivator activator (CoAA) using Sos-Ras Yeast Two-Hybrid screening and thyroid hormone receptor (TR)-binding protein (TRBP)-C-terminus as bait. Interestingly, we obtained a shorter splicing variant, named coactivator modulator (CoAM). Both CoAA and CoAM contain RNA-recognition motifs (RRMs) in their N-termini. An In vitro PolyA RNA-protein interacting assay showed a broad specificity of CoAA/CoAM with native RNAs. Transient transfection-based reporter assays showed that the glucocorticoid rceptor (GR)-mediated transcription activated by a series of coactivators were completely repressed by adding CoAM. CoAM suppressed AP-1 -mediated transcription in CV-1 cells, suggesting that CoAM functions as a general repressor. A histone deacethylase (HDAC) inhibitor trichostatin A (TSA) did not affect on the CoAM-mediated transcriptional repression through thyroid hormone response element (TRE) in CV-1 cells, suggesting that the repression by CoAM may not due to recruitment of HDACs. On the other hand, twice as much as CoAM did not fully repressed the CoAA activated transcription. These results suggest that a ratio of CoAM versus CoAA in nucleus might determine the level of transcription. Resent study revealed that CoAA functions not only as a transcriptional coactivator but also as a splicing activator. Taken together, the ratio of CoAM versus CoAA may regulate the level of protein product by controlling gene expression and processing at multiple levels. [Jpn J Physiol 55 Suppl:S209 (2005)]
