Role of the RNA-binding protein Nrd1 and Pmk1 mitogen-activated protein kinase in the regulation of myosin mRNA stability in fission yeast.
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.
Satoh
Ryosuke
R
Laboratory of Molecular Pharmacogenomics, and Laboratory of Pharmaceutical Analytical Chemistry, School of Pharmaceutical Sciences, Kinki University, Higashi-Osaka 577-8502, Japan.
Morita
Takahiro
T
Takada
Hirofumi
H
Kita
Ayako
A
Ishiwata
Shunji
S
Doi
Akira
A
Hagihara
Kanako
K
Taga
Atsushi
A
Matsumura
Yasuhiro
Y
Tohda
Hideki
H
Sugiura
Reiko
R
D000595:Amino Acid Sequence; D001483:Base Sequence; D048749:Cytokinesis; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D017353:Gene Deletion; D018628:Gene Dosage; D015966:Gene Expression Regulation, Fungal; D016153:Genes, Suppressor; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008969:Molecular Sequence Data; D009218:Myosins / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D020871:RNA Stability; D012261:Ribonucleoproteins / Q000737:chemistry / Q000378:metabolism*; D012568:Schizosaccharomyces / Q000166:cytology / Q000201:enzymology* / Q000235:genetics; D029702:Schizosaccharomyces pombe Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
D003598:Cytoskeletal Proteins; D012261:Ribonucleoproteins; D029702:Schizosaccharomyces pombe Proteins; C513274:cdc4 protein, S pombe; C491210:nrd1 protein, S pombe; D020928:Mitogen-Activated Protein Kinases; C516338:Pmk1 protein, S pombe; D009218:Myosins