U7 snRNA acts as a transcriptional regulator interacting with an inverted CCAAT sequence-binding transcription factor NF-Y.
An inverted CCAAT sequence is recognized by both transcription factors NF-Y and DNA/RNA binding protein YB-1. In the process of examining the effect of nuclear RNA on an inverted CCAAT-containing promoter of MDR1 gene, we found that U7 snRNA inhibits NF-Y and suppresses the promoter activity both in vitro and in NG108-15 tumor cells. Analysis using a designed RNA, which was structurally unrelated to U7 snRNA, revealed that RNA binding by YB-1 is not specific and that the protein is not involved in the transcription. Furthermore, we demonstrated that in the nucleus of doxorubicin-treated cells, DNA binding by NF-Y and transcriptional activity of the promoter were inhibited without either a decrease of NF-Y or an increase of the p53 tumor suppressor, which is known to inhibit DNA binding by NF-Y. In these cells, U7 snRNA was specifically increased and associated with NF-Y, and treatment with RNase A eliminated the inhibition of NF-Y activity. These results suggest that U7 snRNA has a novel function as a transcriptional regulator to control NF-Y.
Higuchi
Takashi
T
Department of Biochemistry, College of Pharmacy, Nihon University, 7-7-1, Narashinodai, Funabashi, Chiba 274-8555, Japan.
Anzai
Kaijiro
K
Kobayashi
Shunsuke
S
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D023081:CCAAT-Binding Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D045744:Cell Line, Tumor; D005786:Gene Expression Regulation; D051379:Mice; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000235:genetics; D012342:RNA, Small Nuclear / Q000378:metabolism*; D014158:Transcription, Genetic
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D023081:CCAAT-Binding Factor; D012342:RNA, Small Nuclear; C405487:U7 small nuclear RNA