title: Role of the RNA-binding protein Nrd1 in stress granule formation and its implication in the stress response in fission yeast.
abstract: 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, Nrd1(DD) (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.
authors.affiliation: Laboratory of Molecular Pharmacogenomics, School of Pharmaceutical Sciences, Kinki University, Osaka, Japan.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Satoh
authors.forename: Akitomo
authors.initials: A
authors.lastname: Tanaka
authors.forename: Ayako
authors.initials: A
authors.lastname: Kita
authors.forename: Takahiro
authors.initials: T
authors.lastname: Morita
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Matsumura
authors.forename: Nanae
authors.initials: N
authors.lastname: Umeda
authors.forename: Makoto
authors.initials: M
authors.lastname: Takada
authors.forename: Sachiko
authors.initials: S
authors.lastname: Hayashi
authors.forename: Tokio
authors.initials: T
authors.lastname: Tani
authors.forename: Kaori
authors.initials: K
authors.lastname: Shinmyozu
authors.forename: Reiko
authors.initials: R
authors.lastname: Sugiura
mesh_terms: D018053:Arsenites / Q000494:pharmacology; D019256:Cadmium Chloride / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D012331:RNA, Fungal / Q000378:metabolism; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface / Q000378:metabolism; D012261:Ribonucleoproteins / Q000378:metabolism*; D012568:Schizosaccharomyces / Q000187:drug effects / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000378:metabolism*; D017670:Sodium Compounds / Q000494:pharmacology; D013696:Temperature
chemical_list: D018053:Arsenites; D012331:RNA, Fungal; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface; D012261:Ribonucleoproteins; D029702:Schizosaccharomyces pombe Proteins; D017670:Sodium Compounds; C000617313:cpc2 protein, S pombe; C491210:nrd1 protein, S pombe; C017947:sodium arsenite; D011189:Potassium Chloride; D006861:Hydrogen Peroxide; D019256:Cadmium Chloride