Role of the RNA-binding protein Nrd1 in stress granule formation and its implication in the stress response in fission yeast.
Role of the RNA-binding protein Nrd1 in stress granule formation and its implication in the stress response in fission yeast.
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DOI：
10.1371/journal.pone.0029683
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Sugiura R
中科院分区：
文献类型：
--
作者：
Satoh R;Tanaka A;Kita A;Morita T;Matsumura Y;Umeda N;Takada M;Hayashi S;Tani T;Shinmyozu K;Sugiura R
我们以前已经确定了RNA识别基序（RRM）型RNA结合蛋白Nrd 1作为一个重要的调节肌球蛋白在裂变酵母的转录后表达。Pmk 1 MAPK依赖性磷酸化负调节Nrd 1的RNA结合活性。在这里，我们报告的Nrd 1在应力诱导的RNA颗粒的作用。Nrd 1可以定位于poly（A）-binding protein（Pabp）阳性的RNA颗粒，以响应各种应激刺激，包括热休克、亚砷酸盐处理和氧化应激。有趣的是，与非磷酸化的Nrd 1相比，Nrd 1DD（Nrd 1的磷酸化模拟版本）在各种刺激下更快地从细胞质易位到应激颗粒;这表明MAPK对Nrd 1的磷酸化增强了其在应激诱导的细胞质颗粒中的定位。Nrd 1以磷酸化依赖的方式与Cpc 2（裂殖酵母RACK）结合，Cpc 2的缺失会影响亚砷酸盐处理后Nrd 1阳性颗粒的形成。此外，Nrd 1的耗竭导致Pabp阳性RNA颗粒形成的延迟，并且Nrd 1的过表达导致Pabp阳性颗粒的大小和数量增加。有趣的是，Nrd 1缺失诱导的持续应力和增强的敏感性，瞬时应力的抗性。总之，我们的研究结果表明，Nrd 1在应力诱导的颗粒形成中发挥作用，这影响了裂殖酵母的抗应力能力。
We have previously identified the RNA recognition motif (RRM)-type RNA-binding protein Nrd1 as an important regulator of the posttranscriptional expression of myosin in fission yeast. Pmk1 MAPK-dependent phosphorylation negatively regulates the RNA-binding activity of Nrd1. Here, we report the role of Nrd1 in stress-induced RNA granules. Nrd1 can localize to poly(A)-binding protein (Pabp)-positive RNA granules in response to various stress stimuli, including heat shock, arsenite treatment, and oxidative stress. Interestingly, compared with the unphosphorylatable Nrd1, Nrd1DD (phosphorylation-mimic version of Nrd1) translocates more quickly from the cytoplasm to the stress granules in response to various stimuli; this suggests that the phosphorylation of Nrd1 by MAPK enhances its localization to stress-induced cytoplasmic granules. Nrd1 binds to Cpc2 (fission yeast RACK) in a phosphorylation-dependent manner and deletion of Cpc2 affects the formation of Nrd1-positive granules upon arsenite treatment. Moreover, the depletion of Nrd1 leads to a delay in Pabp-positive RNA granule formation, and overexpression of Nrd1 results in an increased size and number of Pabp-positive granules. Interestingly, Nrd1 deletion induced resistance to sustained stresses and enhanced sensitivity to transient stresses. In conclusion, our results indicate that Nrd1 plays a role in stress-induced granule formation, which affects stress resistance in fission yeast.
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