A large intergenic noncoding RNA induced by p53 mediates global gene repression in the p53 response.
A large intergenic noncoding RNA induced by p53 mediates global gene repression in the p53 response.
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DOI：
10.1016/j.cell.2010.06.040
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发表时间：
2010-08-06
期刊：
影响因子：
64.5
通讯作者：
Rinn JL
中科院分区：
文献类型：
--
作者：
Huarte M;Guttman M;Feldser D;Garber M;Koziol MJ;Kenzelmann-Broz D;Khalil AM;Zuk O;Amit I;Rabani M;Attardi LD;Regev A;Lander ES;Jacks T;Rinn JL
最近，已有一千多个大的基因间非编码RNA(LincRNAs)被报道。这些RNA在哺乳动物基因组中进化上是保守的，因此可能在不同的生物过程中发挥作用。在这里，我们报告了受p53调控的lincRNAs的鉴定。其中一个lincRNAs(lincRNA-p21)在p53依赖的转录反应中起抑制作用。抑制lincRNA-p21影响数百个基因靶点的表达，这些基因靶点通常由p53抑制。观察到的lincRNA-p21的转录抑制是通过与hnRNP-K的物理结合而介导的。这种相互作用对于hnRNP-K在被抑制基因上的适当基因组定位和对P53介导的细胞凋亡的调控是必需的。我们提出了一个模型，转录因子通过与抑制复合体物理结合并调节它们的定位到先前活跃的基因集来激活作为关键抑制物的lincRNAs。
Recently, more than a thousand large intergenic non-coding RNAs (lincRNAs) have been reported. These RNAs are evolutionarily conserved in mammalian genomes and thus presumably function in diverse biological processes. Here, we report the identification of lincRNAs that are regulated by p53. One of these lincRNAs (lincRNA-p21) serves as a repressor in p53-dependent transcriptional responses. Inhibition of lincRNA-p21 affects the expression of hundreds of gene targets enriched for genes normally repressed by p53. The observed transcriptional repression by lincRNA-p21 is mediated through the physical association with hnRNP-K. This interaction is required for proper genomic localization of hnRNP-K at repressed genes and regulation of p53 mediated apoptosis. We propose a model whereby transcription factors activate lincRNAs that serve as key repressors by physically associating with repressive complexes and modulating their localization to sets of previously active genes.
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