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Updated: Aug 13, 2026

Monitoring Protein-RNA Interaction Dynamics In Vivo at High Temporal Resolution Using χCRAC
Published on: May 9, 2020
Cip1 and Cip2 are novel RNA-recognition-motif proteins that counteract Csx1 function during oxidative stress
Victoria Martín1, Miguel A Rodríguez-Gabriel, W Hayes McDonald
1Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Abstract:
Eukaryotic cells reprogram their global patterns of gene expression in response to stress. Recent studies in Schizosaccharomyces pombe showed that the RNA-binding protein Csx1 plays a central role in controlling gene expression during oxidative stress. It does so by stabilizing atf1(+) mRNA, which encodes a subunit of a bZIP transcription factor required for gene expression during oxidative stress. Here, we describe two related proteins, Cip1 and Cip2, that were identified by multidimensional protein identification technology (MudPIT) as proteins that coprecipitate with Csx1. Cip1 and Cip2 are cytoplasmic proteins that have RNA recognition motifs (RRMs). Neither protein is essential for viability, but a cip1Delta cip2Delta strain grows poorly and has altered cellular morphology. Genetic epistasis studies and whole genome expression profiling show that Cip1 and Cip2 exert posttranscriptional control of gene expression in a manner that is counteracted by Csx1. Notably, the sensitivity of csx1Delta cells to oxidative stress and their inability to induce expression of Atf1-dependent genes are partially rescued by cip1Delta and cip2Delta mutations. This study emphasizes the importance of a modulated mRNA stability in the eukaryotic stress response pathways and adds new information to the role of RNA-binding proteins in the oxidative stress response.
Insights
Two RNA-binding proteins, Cip1 and Cip2, regulate gene expression during oxidative stress in yeast. They counteract Csx1
Area of Science:
- Molecular Biology
- Cell Biology
- Genetics
Background:
- Eukaryotic cells alter gene expression in response to stress.
- The RNA-binding protein Csx1 is crucial for oxidative stress response in Schizosaccharomyces pombe.
- Csx1 stabilizes atf1(+) mRNA, essential for oxidative stress gene expression.
Purpose of the Study:
- Identify novel proteins interacting with Csx1.
- Investigate the function of Cip1 and Cip2 in oxidative stress response.
- Elucidate the interplay between Csx1, Cip1, and Cip2 in posttranscriptional regulation.
Main Methods:
- Multidimensional protein identification technology (MudPIT) for protein identification.
- Genetic epistasis studies to determine genetic interactions.
- Whole genome expression profiling to analyze gene expression changes.
- Analysis of cellular morphology and growth rates.
Main Results:
- Cip1 and Cip2 were identified as Csx1-interacting proteins.
- Cip1 and Cip2 are cytoplasmic proteins with RNA recognition motifs (RRMs).
- Loss of Cip1 and Cip2 leads to poor growth and altered morphology.
- Cip1 and Cip2 negatively regulate gene expression, counteracted by Csx1.
- Mutations in cip1 and cip2 partially rescue the oxidative stress sensitivity of csx1Δ cells.
Conclusions:
- Cip1 and Cip2 play a significant role in posttranscriptional control of gene expression during oxidative stress.
- The balance between Csx1 and Cip1/Cip2 activity is critical for modulating mRNA stability and cellular response to stress.
- This study highlights the complex regulatory network involving RNA-binding proteins in eukaryotic stress response pathways.
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