Human U1 and U6 snRNA genes are transcribed by RNA polymerases II and III, respectively. While the p53 tumor suppressor protein is a general repressor of RNA polymerase III transcription, whether p53 regulates snRNA gene transcription by RNA polymerase II is uncertain. The data presented herein indicate that p53 is an effective repressor of snRNA gene transcription by both polymerases. Both U1 and U6 transcription in vitro is repressed by recombinant p53, and endogenous p53 occupancy at these promoters is stimulated by UV light. In response to UV light, U1 and U6 transcription is strongly repressed. Human U1 genes, but not U6 genes, contain a high-affinity p53 response element located within the core promoter region. Nonetheless, this element is not required for p53 repression and mutant p53 molecules that do not bind DNA can maintain repression, suggesting a reliance on protein interactions for p53 promoter recruitment. Recruitment may be mediated by the general transcription factors TATA-box binding protein and snRNA-activating protein complex, which interact well with p53 and function for both RNA polymerase II and III transcription.The p53 tumor suppressor protein plays a critical role in preventing unwarranted cellular proliferation by activating transcription of key target genes that influence cell growth and apoptosis (reviewed in references 28, 31, 35, and 64). Though p53 can enable both pathways, the switch controlling which cellular outcome is enacted is uncertain (reviewed in references 65 and 66), but both the p53 level and the nature of the DNA damage can influence apoptotic response (8). Altogether, p53 activity serves to prevent passage of mutations to daughter cells after DNA damage.Recent evidence suggests that p53 regulates transcription of genes that are not obviously involved in controlling cell cycle arrest or apoptosis. Indeed, p53 can repress RNA polymerase I (3, 72) and III (5, 9) transcription of genes encoding a variety of nontranslated RNAs that play critical roles at numerous points during global gene expression. RNA polymerase III activity is elevated in p53 Ϫ/Ϫ knockout fibroblasts (5) and in a variety of cancer-derived cell lines that lack p53 function (57). However, the mechanism for p53 regulation of RNA polymerase III transcription is controversial. A kinetic analysis of RNA polymerase III repression using p53 expressed from a stably integrated inducible p53 gene suggested that RNA polymerase III repression is mediated indirectly through p53-dependent degradation of TFIIIB (11). In contrast, recombinant p53 can repress in vitro transcription from a variety of RNA polymerase III-specific promoters and can interact with components of the general transcription machinery required for RNA polymerase III transcription (5, 9, 10, 58), indicating that p53 might directly repress transcription by RNA polymerase III.Within the group of genes transcribed by RNA polymerase III, the human snRNA gene family is intriguing because these genes contain similar sets of promoter elements, and yet on...
