Ghanbarian Hossein, Grandjean Valérie, Cuzin François, Rassoulzadegan Minoo
INSERM U636 Nice, France.
Front Genet. 2011 Dec 28;2:95. doi: 10.3389/fgene.2011.00095. eCollection 2011.
Part of the heterodimeric P-TEF-b element of the Pol II transcription machinery, the cyclin-dependent kinase 9 plays a critical role in gene expression. Phosphorylation of several residues in the polymerase is required for elongation of transcript. It determines the rates of transcription and thus, plays a critical role in several differentiation pathways, best documented in heart development. The synthesis and activity of the protein are tightly regulated in a coordinated manner by at least three non-coding RNAs. First, its kinase activity is reversibly inhibited by formation of a complex with the 334 nt 7SK RNA, from which it is released under conditions of stress. Then, heart development requires a maximal rate of synthesis during cardiomyocyte differentiation, followed by a decrease in the differentiated state. The latter is insured by microRNA-mediated translational inhibition. In a third mode of RNA control, increased levels of transcription are induced by small non-coding RNA molecules with sequences homologous to the transcript. Designated paramutation, this epigenetic variation, stable during development, and hereditarily transmitted in a non-Mendelian manner over several generations, is thought to be a response to the inactivation of one of the two alleles by an abnormal recombination event such as insertion of a transposon.
细胞周期蛋白依赖性激酶9是RNA聚合酶II转录机制中异二聚体P-TEF-b元件的一部分，在基因表达中起关键作用。转录本延伸需要聚合酶中几个残基的磷酸化。它决定转录速率，因此在多种分化途径中起关键作用，在心脏发育中记录最为详尽。该蛋白的合成和活性受到至少三种非编码RNA的协同严格调控。首先，其激酶活性通过与334 nt的7SK RNA形成复合物而被可逆抑制，在应激条件下它会从该复合物中释放出来。其次，心脏发育在心肌细胞分化过程中需要最大合成速率，随后在分化状态下会降低。后者通过微小RNA介导的翻译抑制来保证。在第三种RNA调控模式中，与转录本序列同源的小非编码RNA分子会诱导转录水平升高。这种表观遗传变异被称为副突变，在发育过程中稳定，并以非孟德尔方式在几代中遗传传递，被认为是对异常重组事件（如转座子插入）导致的两个等位基因之一失活的一种反应。
