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.
Highlights
Stress granules (SGs) are non-membranous cytoplasmic foci, composed of non-translating messenger ribonucleoproteins that rapidly accumulate in cells exposed to a broad range of environmental stresses, including oxidative, genotoxic, hyperosmotic, or heat shock stresses [1,2,3]
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
Identification of Nrd1 as a component of fission yeast SGs Here, we have presented several lines of evidence demonstrating that Nrd1 plays a role in SG assembly
Summary
Stress granules (SGs) are non-membranous cytoplasmic foci, composed of non-translating messenger ribonucleoproteins (mRNPs) that rapidly accumulate in cells exposed to a broad range of environmental stresses, including oxidative, genotoxic, hyperosmotic, or heat shock stresses [1,2,3]. Several components of SGs have been identified, including the related RNA-binding proteins TIA-1 and TIAR, poly(A)-binding protein (PABP), and translation factors such as eIF3, eIF4E, and eIF4G [4]. The key event leading to the formation of SGs is the stress-induced phosphorylation of the translation initiation factor eIF2a [5]. The assembly of SGs in response to the phosphorylation of eIF2a is dependent on TIA-1 and TIAR; these proteins are key regulators of SG formation and assembly [5]. The structural domains of these proteins required for the assembly of SGs are the RNA recognition motifs (RRMs) at their N-termini and the prionrelated domains at their C-termini. Identification of TIA-1 mRNA targets showed that this protein binds to a U-rich motif localizing preferentially to the 39-untranslated regions of target genes [6]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
