Université de Paris, CNRS, Institut Jacques Monod, F-75006 Paris, France.
Université de Paris, CNRS, Institut Jacques Monod, F-75006 Paris, France.
Cell Rep. 2020 Jul 21;32(3):107942. doi: 10.1016/j.celrep.2020.107942.
A large share of the non-coding transcriptome in yeast is controlled by the Nrd1-Nab3-Sen1 (NNS) complex, which promotes transcription termination of non-coding RNA (ncRNA) genes, and by the nuclear exosome, which limits the steady-state levels of the transcripts produced. How unconstrained ncRNA levels affect RNA metabolism and gene expression are long-standing and important questions. Here, we show that degradation of ncRNAs by the exosome is required for freeing Nrd1 and Nab3 from the released transcript after termination. In exosome mutants, these factors are sequestered by ncRNAs and cannot be efficiently recycled to sites of transcription, inducing termination defects at NNS targets. ncRNA-dependent, genome-wide termination defects can be recapitulated by the expression of a degradation-resistant, circular RNA containing a natural NNS target in exosome-proficient cells. Our results have important implications for the mechanism of termination, the general impact of ncRNAs abundance, and the importance of nuclear ncRNA degradation.
酵母中非编码转录组的很大一部分受 Nrd1-Nab3-Sen1(NNS)复合物控制,该复合物促进非编码 RNA(ncRNA)基因的转录终止,同时受核核酶体控制,核酶体限制了转录产物的稳态水平。ncRNA 水平不受限制如何影响 RNA 代谢和基因表达是一个长期存在且重要的问题。在这里,我们表明,核酶体降解 ncRNA 对于在终止后将 Nrd1 和 Nab3 从释放的转录本中释放出来是必需的。在核酶体突变体中,这些因子被 ncRNA 隔离,不能有效地回收至转录部位,从而在 NNS 靶标处诱导终止缺陷。在核酶体功能正常的细胞中,通过表达含有天然 NNS 靶标的降解抗性环状 RNA,可以重现 ncRNA 依赖性、全基因组终止缺陷。我们的研究结果对终止机制、ncRNA 丰度的普遍影响以及核 ncRNA 降解的重要性具有重要意义。