Salminen Antero, Kaarniranta Kai
Department of Neurology, Institute of Clinical Medicine, University of Kuopio, P.O. Box 1627, FIN-70211 Kuopio, Finland.
Biochem Biophys Res Commun. 2009 Jan 2;378(1):6-9. doi: 10.1016/j.bbrc.2008.11.023. Epub 2008 Nov 21.
Ribosomal RNA (rRNA) genes arrange themselves in a tandem pattern in nucleolus and during the transcription of rRNA genes, the elongating nascent rRNA transcripts create a structure called Christmas tree. rRNA genes in the rDNA locus can be either active or silent depending on the epigenetic regulation of the chromatin structure. Yeast Sir2 (silent information regulator 2) protein containing complexes can repress the recombination in the rDNA locus and subsequently extend the replicative lifespan of the budding yeast. The mammalian rDNA locus is also under the epigenetic regulation by protein complexes, such as NoRC (nucleolar remodeling complex) and eNoSC (energy-dependent nucleolar silencing complex), involving histone deacetylases and methyltransferases. SIRT1, a NAD(+)-dependent histone deacetylase, is the key component in the eNoSC complex and hence energetic changes can regulate the activation of eNoSC complex and in this way mediate the epigenetic silencing of rRNA gene expression. The eNoSC complex links SIRT1-induced longevity regulation to the metabolic rate theory of aging.
核糖体RNA（rRNA）基因在核仁中以串联模式排列，在rRNA基因转录过程中，正在延伸的新生rRNA转录本形成一种称为圣诞树的结构。rDNA位点中的rRNA基因可以是活跃的，也可以是沉默的，这取决于染色质结构的表观遗传调控。含有酵母Sir2（沉默信息调节因子2）蛋白的复合物可以抑制rDNA位点的重组，从而延长芽殖酵母的复制寿命。哺乳动物rDNA位点也受到蛋白质复合物的表观遗传调控，如NoRC（核仁重塑复合物）和eNoSC（能量依赖性核仁沉默复合物），涉及组蛋白脱乙酰酶和甲基转移酶。SIRT1是一种依赖NAD（+）的组蛋白脱乙酰酶，是eNoSC复合物的关键成分，因此能量变化可以调节eNoSC复合物的激活，从而介导rRNA基因表达的表观遗传沉默。eNoSC复合物将SIRT1诱导的寿命调节与衰老的代谢率理论联系起来。
