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lncRNA recruits RNAi and the exosome to dynamically regulate pho1 expression in response to phosphate levels in fission yeast

机译:lncRNA募集RNAi和外泌体以响应裂变酵母中的磷酸盐水平动态调节pho1表达

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摘要

Numerous noncoding transcripts of unknown function have recently been identified. In this study, we report a novel mechanism that relies on transcription of noncoding RNA prt (pho1-repressing transcript) regulating expression of the pho1 gene. A product of this gene, Pho1, is a major secreted phosphatase needed for uptake of extracellular phosphate in fission yeast. prt is produced from the promoter located upstream of the pho1 gene in response to phosphate, and its transcription leads to deposition of RNAi-dependent H3K9me2 across the pho1 locus. In contrast, phosphate starvation leads to loss of H3K9me2 and pho1 induction. Strikingly, deletion of Clr4, a H3K9 methyltransferase, results in faster pho1 induction in response to phosphate starvation. We propose a new role for noncoding transcription in establishing transient heterochromatin to mediate an effective transcriptional response to environmental stimuli. RNAi recruitment to prt depends on the RNA-binding protein Mmi1. Importantly, we found that the exosome complex and Mmi1 are required for transcription termination and the subsequent degradation of prt but not pho1 mRNA. Moreover, in mitotic cells, transcription termination of meiotic RNAs also relies on this mechanism. We propose that exosome-dependent termination constitutes a specialized system that primes transcripts for degradation to ensure their efficient elimination.
机译:最近发现了许多未知功能的非编码转录本。在这项研究中,我们报告了一种新型机制,该机制依赖于非编码RNA prt(pho1抑制转录本)的转录,调节pho1基因的表达。该基因的产物Pho1是在裂变酵母中摄取细胞外磷酸所需的主要分泌型磷酸酶。 prt是由位于pho1基因上游的启动子响应磷酸盐产生的,其转录导致RNAi依赖性H3K9me2在pho1基因座上的沉积。相反,磷酸盐饥饿导致H3K9me2和pho1诱导的损失。令人惊讶的是,H3K9甲基转移酶Clr4的缺失导致响应磷酸盐饥饿而更快地诱导pho1。我们提出非编码转录在建立瞬时异染色质介导对环境刺激的有效转录反应中的新作用。 RNAi募集至prt取决于RNA结合蛋白Mmi1。重要的是,我们发现外泌体复合物和Mmi1是转录终止和prt而不是pho1 mRNA后续降解所必需的。而且,在有丝分裂细胞中,减数分裂RNA的转录终止也依赖于该机制。我们建议依赖外来体的终止构成一个专门的系统,该系统引发转录本降解以确保其有效消除。

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