Mayer Christine, Neubert Melanie, Grummt Ingrid
Division of Molecular Biology of the Cell II, German Cancer Research Center, DKFZ-ZMBH-Alliance, INF 581, D-69120 Heidelberg, Germany.
EMBO Rep. 2008 Aug;9(8):774-80. doi: 10.1038/embor.2008.109. Epub 2008 Jul 4.
Silencing of ribosomal RNA genes (rDNA) requires binding of the chromatin remodelling complex NoRC to RNA that is complementary to the rDNA promoter. NoRC-associated RNA (pRNA) folds into a conserved stem-loop structure that is required for nucleolar localization and rDNA silencing. Mutations that disrupt the stem-loop structure impair binding of TIP5, the large subunit of NoRC, to pRNA and abolish targeting of NoRC to nucleoli. Binding to pRNA results in a conformational change of TIP5, as shown by enhanced sensitivity of TIP5 towards trypsin digestion. Our results indicate an RNA-dependent mechanism that targets NoRC to chromatin and facilitates the interaction with co-repressors that promote heterochromatin formation and rDNA silencing.
核糖体RNA基因(rDNA)的沉默需要染色质重塑复合物NoRC与与rDNA启动子互补的RNA结合。NoRC相关RNA(pRNA)折叠成一种保守的茎环结构,这是核仁定位和rDNA沉默所必需的。破坏茎环结构的突变会损害NoRC的大亚基TIP5与pRNA的结合,并消除NoRC对核仁的靶向作用。与pRNA的结合导致TIP5的构象变化,如TIP5对胰蛋白酶消化的敏感性增强所示。我们的结果表明了一种RNA依赖性机制,该机制将NoRC靶向染色质,并促进与促进异染色质形成和rDNA沉默的共抑制因子的相互作用。