Role of the RNA-binding Protein Nrd1 and Pmk1 Mitogen-activated Protein Kinase in the Regulation of Myosin mRNA Stability in Fission Yeast
Role of the RNA-binding Protein Nrd1 and Pmk1 Mitogen-activated Protein Kinase in the Regulation of Myosin mRNA Stability in Fission Yeast
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DOI：
10.1091/mbc.e08-09-0893
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发表时间：
2009-05-01
影响因子：
3.3
通讯作者：
Sugiura, Reiko
中科院分区：
文献类型：
--
作者：
Satoh, Ryosuke;Morita, Takahiro;Sugiura, Reiko
肌球蛋白 II 是肌动球蛋白收缩环的重要组成部分，通过产生肌动球蛋白环收缩所需的力，在胞质分裂中发挥着至关重要的作用。 Cdc4 是裂殖酵母中必需的肌球蛋白 II 轻链，是胞质分裂所必需的。在各种真核生物中，肌球蛋白的磷酸化被充分证明是激活肌球蛋白 II 的主要手段，但人们对 Cdc4 的调节机制知之甚少。在这里，我们分离了 Nrd1，一种具有 RNA 识别基序的 RNA 结合蛋白，作为 cdc4 突变体的多拷贝抑制子。值得注意的是，我们证明 Nrd1 结合并稳定 Cdc4 mRNA，从而抑制 cdc4 突变体的胞质分裂缺陷。重要的是，Pmk1 丝裂原激活蛋白激酶 (MAPK) 直接磷酸化 Nrd1，从而负向调节 Nrd1 与 Cdc4 mRNA 的结合活性。一致地，Pmk1 MAPK 信号传导的失活以及 Nrd1 的过表达稳定了 Cdc4 mRNA 水平，从而抑制了与 cdc4 突变体相关的胞质分裂缺陷。此外，我们还证明了 Pmk1/Nrd1 信号传导的细胞周期依赖性调节。总之，我们的结果表明 Nrd1 在调节 Cdc4 mRNA 稳定性中发挥作用；此外，我们的研究首次证明了 MAPK 信号传导对肌球蛋白表达的转录后调节。
Myosin II is an essential component of the actomyosin contractile ring and plays a crucial role in cytokinesis by generating the forces necessary for contraction of the actomyosin ring. Cdc4 is an essential myosin II light chain in fission yeast and is required for cytokinesis. In various eukaryotes, the phosphorylation of myosin is well documented as a primary means of activating myosin II, but little is known about the regulatory mechanisms of Cdc4. Here, we isolated Nrd1, an RNA-binding protein with RNA-recognition motifs, as a multicopy suppressor of cdc4 mutants. Notably, we demonstrated that Nrd1 binds and stabilizes Cdc4 mRNA, thereby suppressing the cytokinesis defects of the cdc4 mutants. Importantly, Pmk1 mitogen-activated protein kinase (MAPK) directly phosphorylates Nrd1, thereby negatively regulating the binding activity of Nrd1 to Cdc4 mRNA. Consistently, the inactivation of Pmk1 MAPK signaling, as well as Nrd1 overexpression, stabilized the Cdc4 mRNA level, thereby suppressing the cytokinesis defects associated with the cdc4 mutants. In addition, we demonstrated the cell cycle-dependent regulation of Pmk1/Nrd1 signaling. Together, our results indicate that Nrd1 plays a role in the regulation of Cdc4 mRNA stability; moreover, our study is the first to demonstrate the posttranscriptional regulation of myosin expression by MAPK signaling.