Transcription termination and RNA degradation contribute to silencing of RNA polymerase II transcription within heterochromatin
Transcription termination and RNA degradation contribute to silencing of RNA polymerase II transcription within heterochromatin
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DOI：
10.1016/j.molcel.2008.01.011
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发表时间：
2008-02-15
期刊：
影响因子：
16
通讯作者：
Buratowski, Stephen
中科院分区：
文献类型：
--
作者：
Vasilieva, Lidia;Kim, Minkyu;Buratowski, Stephen
在芽殖酵母的异染色质中，RNA聚合酶II（RNAPII）的转录被Sir 2脱乙酰酶抑制。尽管异染色质沉默通常被认为是由于潜在DNA的可及性有限，但有几份关于沉默区域内RNAPII和基础转录因子的报告。rDNA阵列的分析揭示了“非转录”间隔区内的隐蔽RNAPII转录。这些转录物由Nrd 1/Sen 1复合物终止并由外泌体降解。该途径中的突变导致rDNA基因座中的沉默减少和显着的染色质变化。有趣的是，Nrd 1突变体也显示出更高水平的rDNA重组，这表明隐藏的RNAPII转录可能在调节rDNA拷贝数方面具有生理作用。Nrd 1/Sen 1/exosome途径也有助于端粒位点的沉默。这些结果表明，在酿酒酵母异染色质基因的沉默发生在转录和转录后水平。
Within the heterochromatin of budding yeast, RNA polymerase II (RNAPII) transcription is repressed by the Sir2 deacetylase. Although heterochromatic silencing is generally thought to be due to limited accessibility of the underlying DNA, there are several reports of RNAPII and basal transcription factors within silenced regions. Analysis of the rDNA array revealed cryptic RNAPII transcription within the "non-transcribed" spacer region. These transcripts are terminated by the Nrd1 /Sen1 complex and degraded by the exosome. Mutations in this pathway lead to decreased silencing and dramatic chromatin changes in the rDNA locus. Interestingly, Nrd1 mutants also show higher levels of rDNA recombination, suggesting that the cryptic RNAPII transcription might have a physiological role in regulating rDNA copy number. The Nrd1/Sen1/exosome pathway also contributes to silencing at telomeric loci. These results suggest that silencing of heterochromatic genes in Saccharomyces cerevisiae occurs at both transcriptional and posttranscriptional levels.