The p53 tumor suppressor protein represses human snRNA gene transcription by RNA polymerases II and III independently of sequence-specific DNA binding.
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.
Gridasova
Anastasia A
AA
Department of Biochemistry & Molecular Biology, Michigan State University, East Lansing, MI 48824. henryrw@msu.edu.
Henry
R William
RW
D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D015536:Down-Regulation; D006801:Humans; D011401:Promoter Regions, Genetic / Q000235:genetics; D012319:RNA Polymerase II / Q000037:antagonists & inhibitors* / Q000502:physiology; D012320:RNA Polymerase III / Q000037:antagonists & inhibitors* / Q000502:physiology; D012342:RNA, Small Nuclear / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D020218:Response Elements / Q000235:genetics; D035181:TATA-Box Binding Protein / Q000502:physiology; D014158:Transcription, Genetic / Q000528:radiation effects; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D014466:Ultraviolet Rays
D004268:DNA-Binding Proteins; D012342:RNA, Small Nuclear; D012097:Repressor Proteins; D035181:TATA-Box Binding Protein; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C405483:U1 small nuclear RNA; C405486:U6 small nuclear RNA; D012319:RNA Polymerase II; D012320:RNA Polymerase III