Stress-induced inhibition of mRNA export triggers RNase III-mediated decay of the BDF2 mRNA.
Stress-induced inhibition of mRNA export triggers RNase III-mediated decay of the BDF2 mRNA.
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DOI：
10.1261/rna.078880.121
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发表时间：
2021-12
期刊：
影响因子：
--
通讯作者：
Chanfreau GF
中科院分区：
文献类型：
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作者：
Wang C;Barr K;Neutel D;Roy K;Liu Y;Chanfreau GF
调节染色质结构和可接近性的含溴结构域蛋白的表达必须严格控制以确保基因表达的适当调节。在酵母S.在酿酒酵母中，溴结构域因子2（BDF 2）的表达在应激期间通过RNA酶III介导的衰变（RMD）在转录后被广泛调节，所述RMD通过RNA酶III同源物Rnt1p切割细胞核中的BDF 2 mRNA而触发。先前的研究表明，RMD介导的BDF2下调在渗透胁迫条件下被过度激活，但在这些条件下驱动BDF2 RNA核切割增强的机制仍然未知。在这里，我们表明，RMD超活化可以检测到在多种胁迫条件下，抑制mRNA的出口，和Rnt1p仍然主要定位在细胞核在盐胁迫。我们发现，在没有压力的情况下，通过锚定远离mRNA生物合成或输出因子出核来全面抑制mRNA核输出可以重演RMD超激活。RMD超活化需要Rnt1p核定位，但不依赖于BDF2基因的内源性启动子，其效率受Rnt1p切割的茎环结构的影响。由于多种应激条件已被证明介导mRNA输出的全局抑制，我们的研究结果表明，RMD的超活化主要是应激期间BDF2 mRNA的核保留增加的结果。
The expression of bromodomain-containing proteins that regulate chromatin structure and accessibility must be tightly controlled to ensure the appropriate regulation of gene expression. In the yeast S. cerevisiae, Bromodomain Factor 2 (BDF2) expression is extensively regulated post-transcriptionally during stress by RNase III-mediated decay (RMD), which is triggered by cleavage of the BDF2 mRNA in the nucleus by the RNase III homolog Rnt1p. Previous studies have shown that RMD-mediated down-regulation of BDF2 is hyperactivated in osmotic stress conditions, yet the mechanisms driving the enhanced nuclear cleavage of BDF2 RNA under these conditions remain unknown. Here, we show that RMD hyperactivation can be detected in multiple stress conditions that inhibit mRNA export, and that Rnt1p remains primarily localized in the nucleus during salt stress. We show that globally inhibiting mRNA nuclear export by anchoring away mRNA biogenesis or export factors out of the nucleus can recapitulate RMD hyperactivation in the absence of stress. RMD hyperactivation requires Rnt1p nuclear localization but does not depend on the BDF2 gene endogenous promoter, and its efficiency is affected by the structure of the stem–loop cleaved by Rnt1p. Because multiple stress conditions have been shown to mediate global inhibition of mRNA export, our results suggest that the hyperactivation of RMD is primarily the result of the increased nuclear retention of the BDF2 mRNA during stress.