Activation function-1 domain of androgen receptor contributes to the interaction between subnuclear splicing factor compartment and nuclear receptor compartment. Identification of the p102 U5 small nuclear ribonucleoprotein particle-binding protein as a coactivator for the receptor.
In the androgen receptor (AR), most of its transactivation activity is mediated via the activation function-1 (AF-1). By employing yeast two-hybrid assay, we isolated a cDNA sequence encoding a protein binding to AR-AF-1. This protein, named ANT-1 (AR N-terminal domain transactivating protein-1), enhanced the ligand-independent autonomous AF-1 transactivation function of AR or glucocorticoid receptor but did not enhance that of estrogen receptor alpha. In contrast, the ANT-1 did not enhance any ligand-dependent AF-2 activities. Furthermore, the ligand-independent interaction between AR-AF-1 and ANT-1 was confirmed in vivo and in vitro. The ANT-1 sequence was identical to that of a protein that binds to U5 small nuclear ribonucleoprotein particle, a human homologue of yeast splicing factor Prp6p, involved in spliceosome. ANT-1 was compartmentalized into 20-40 coarse splicing factor compartment speckles against the background of the diffuse reticular distribution. AR colocalized with ANT-1 only in the diffusely distributed area, whereas the ANT-1 speckles were spatially distinct from but surrounded by the AR compartments. The active gene transcription has been shown to couple simultaneously with pre-mRNA processing at the periphery of the splicing factor compartment. The molecular interaction between two spatially distinct subnuclear compartments mediated by ANT-1 may therefore recruit AR into the transcription-splicing-coupling machinery.
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