title: p53-Dependent induction of PVT1 and miR-1204.
abstract: p53 is a tumor suppressor protein that acts as a transcription factor to regulate (either positively or negatively) a plethora of downstream target genes. Although its ability to induce protein coding genes is well documented, recent studies have implicated p53 in the regulation of non-coding RNAs, including both microRNAs (e.g. miR-34a) and long non-coding RNAs (e.g. lincRNA-p21). We have identified the non-protein coding locus PVT1 as a p53-inducible target gene. PVT1, a very large (>300 kb) locus located downstream of c-myc on chromosome 8q24, produces a wide variety of spliced non-coding RNAs as well as a cluster of six annotated microRNAs: miR-1204, miR-1205, miR-1206, miR-1207-5p, miR-1207-3p, and miR-1208. Chromatin immunoprecipitation (ChIP), electrophoretic mobility shift assay (EMSA), and luciferase assays reveal that p53 binds and activates a canonical response element within the vicinity of miR-1204. Consistently, we demonstrate the p53-dependent induction of endogenous PVT1 transcripts and consequent up-regulation of mature miR-1204. Finally, we have shown that ectopic expression of miR-1204 leads to increased p53 levels and causes cell death in a partially p53-dependent manner.
authors: Department of Biological Sciences, Columbia University, New York, New York 10027, USA.
authors: Anthony M
authors: AM
authors: Barsotti
authors: Rachel
authors: R
authors: Beckerman
authors: Oleg
authors: O
authors: Laptenko
authors: Konrad
authors: K
authors: Huppi
authors: Natasha J
authors: NJ
authors: Caplen
authors: Carol
authors: C
authors: Prives
mesh_terms: D016923:Cell Death / Q000502:physiology; D045744:Cell Line, Tumor; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics / Q000378:metabolism*; D056426:Genetic Loci / Q000502:physiology; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012323:RNA Processing, Post-Transcriptional / Q000502:physiology; D062085:RNA, Long Noncoding; D020218:Response Elements / Q000502:physiology*; D014158:Transcription, Genetic / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: C582273:MIRN1206 microRNA, human; D035683:MicroRNAs; C521123:PVT1 long-non-coding RNA, human; D011506:Proteins; D062085:RNA, Long Noncoding; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53