p53 诱导的一个大型基因间非编码 RNA 介导 p53 应答中的全基因组基因沉默。
A large intergenic noncoding RNA induced by p53 mediates global gene repression in the p53 response.
机构信息
The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
出版信息
Cell. 2010 Aug 6;142(3):409-19. doi: 10.1016/j.cell.2010.06.040.
Recently, more than 1000 large intergenic noncoding 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 mediates apoptosis. We propose a model whereby transcription factors activate lincRNAs that serve as key repressors by physically associating with repressive complexes and modulate their localization to sets of previously active genes.
最近，已经报道了超过 1000 个大型基因间非编码 RNA（lincRNA）。这些 RNA 在哺乳动物基因组中是进化保守的，因此推测在多种生物学过程中发挥作用。在这里，我们报告了受 p53 调控的 lincRNA 的鉴定。其中一个 lincRNA（lincRNA-p21）作为 p53 依赖性转录反应中的抑制剂。抑制 lincRNA-p21 会影响数百个基因靶标（通常受 p53 抑制）的表达。通过与 hnRNP-K 的物理结合来介导 lincRNA-p21 的观察到的转录抑制。这种相互作用对于 hnRNP-K 在受抑制基因上的正确基因组定位和 p53 介导的凋亡的调节是必需的。我们提出了一个模型，即转录因子通过与抑制复合物物理结合来激活 lincRNA，作为关键抑制剂，并调节它们到先前活跃基因的集合的定位。
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