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, 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.

Genome‐wide identification, evolution, and expression analysis of RNA‐binding glycine‐rich protein family in maize

“…For instance, when serines in the RRM termini were phosphorylated, SRSF1 (aka ASF/SF2) appeared to induce a key molecular switch from intra‐ to inter‐molecular interactions during pre‐mRNA splicing (Cho et al ). In addition, the phosphorylation of Nrd1 could enhance its localization to stress‐induced cytoplasmic granules in fission yeast (Satoh et al ). In this study, most (18) of the 23 ZmRB‐GRPs were predicted to contain 1 to 13 phosphorylation residues, and the residues and their locations were generally different in different classes (Figure ), suggesting function of the genes in different classes are varied.…”

Skb5, an SH3 adaptor protein, regulates Pmk1 MAPK signaling by controlling the intracellular localization of Mkh1 MAPKKK

“…fluorescence microscopy) were carried out as described previously (Kita et al, 2004;Satoh et al, 2012). Photographs were taken using an AxioImager M1 microscope (Carl Zeiss, Germany) equipped with an LSM700 microscope (Carl Zeiss) and ZEN 2012 software (Carl Zeiss).…”

A Stress-Activated, p38 Mitogen-Activated Protein Kinase–ATF/CREB Pathway Regulates Posttranscriptional, Sequence-Dependent Decay of Target RNAs

“…One key cellular response to stress in diverse species is the dynamic shuttling of mRNAs and translation factors from polysomes, plus other proteins of RNA metabolism not known to be associated with polysomes, to cytoplasmic granules (for reviews, see references 57, 58, and 59). Stress-induced cytoplasmic granules exist in fission yeast, and they contain mRNAs and orthologs of proteins known to exist in stress granules (SGs) and processing bodies (PBs) of mammals (60)(61)(62)(63)(64). The fission yeast p38 SAPK Spc1 regulates formation of these SGs/PBs (61).…”