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PABPC1 SUMOylation enhances cell survival by promoting mitophagy through stabilizing U-rich mRNAs within stress granules (RIP-Seq)

ABSTRACT: Under cellular stress conditions, translationally stalled mRNAs and associated proteins coalesce into stress granules (SGs), intricately regulating gene expression. Small Ubiquitin-like Modifier (SUMO) modification plays important role in SG dynamics but its function is yet not fully understood. Here, we report that SUMOylation of Poly(A)-Binding Protein Cytoplasmic 1 (PABPC1), a pivotal SG constituent, is dynamically regulated by a variety of stress stimuli, including oxidative, heat, osmotic, and nutritional stresses, facilitating SG assembly. Crucially, we demonstrate that SUMOylation of PABPC1 stabilizes mRNAs bearing conserved U-rich elements under stress, thus preserving their stability. Mechanistically, SUMOylated PABPC1 enhances its interaction with TIA1, a process pivotal for the selectively recognition and recruitment of U-rich mRNAs into SGs, thereby safeguarding these transcripts. Notably, our study reveals that the SUMOylation of PABPC1 stabilizes transcripts critical to the mitophagy pathway, thereby enhancing mitophagy in response to stress and then contributing to the maintenance of cellular homeostasis and enhancing the tumor cell survival under adverse conditions.

ORGANISM(S): Homo sapiens

PROVIDER: GSE260510 | GEO | 2025/05/10

REPOSITORIES: GEO

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PABPC1 SUMOylation enhances cell survival by promoting mitophagy through stabilizing U-rich mRNAs within stress granules (4sU-Seq)

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G3BP1-linked mRNA partitioning supports selective protein synthesis in response to oxidative stress

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