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Originally published as MBC in Press, 10.1091/mbc.E08-09-0893 on March 11, 2009

Vol. 20, Issue 9, 2473-2485, May 1, 2009

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Role of the RNA-binding Protein Nrd1 and Pmk1 Mitogen-activated Protein Kinase in the Regulation of Myosin mRNA Stability in Fission Yeast

Ryosuke Satoh*,{dagger}, Takahiro Morita*,{dagger}, Hirofumi Takada*, Ayako Kita*, Shunji Ishiwata*, Akira Doi*, Kanako Hagihara*, Atsushi Taga{ddagger}, Yasuhiro Matsumura*, Hideki Tohda§, and Reiko Sugiura*

*Laboratory of Molecular Pharmacogenomics, and {ddagger}Laboratory of Pharmaceutical Analytical Chemistry, School of Pharmaceutical Sciences, Kinki University, Higashi-Osaka 577-8502, Japan; and §ASPEX Division, Research Center, Asahi Glass Co. Ltd., Yokohama 221-8755, Japan

Submitted September 2, 2008; Revised February 20, 2009; Accepted February 26, 2009
Monitoring Editor: Patrick J. Brennwald

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.


This article was published online ahead of print in MBC in Press (http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E08-09-0893) on March 11, 2009.

{dagger} These authors contributed equally to this work.

Address correspondence to: Reiko Sugiura (sugiurar{at}phar.kindai.ac.jp)

Abbreviations used: MAPK, mitogen-activated protein kinase; EMM, Edinburgh minimal medium; YPD, yeast extract-peptone-dextrose; GFP, green fluorescent protein; ORF, open reading frame; GST, glutathione-S-transferase




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