2. Academic Validation
  3. PABPC1 SUMOylation enhances cell survival by promoting mitophagy through stabilizing U-rich mRNAs within stress granules

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

  • Nat Commun. 2025 Aug 7;16(1):7308. doi: 10.1038/s41467-025-62619-8.
Caihu Huang # 1 2,  Jiayi Huang # 1,  Runhui Lu # 1,  Ari Jiazhuo Yu 3,  Arno Shengzhuo Yu 3,  Yingting Cao 1,  Lian Li 1,  Junya Li 1,  Hongyan Li 1,  Zihan Zhou 1,  Yixin Zhang 1,  Anan Xu 1,  Ran Chen 1,  Yanli Wang 1,  Xian Zhao 1,  Jian Huang 1,  Yujie Fu 4,  Ming Xu 5,  Hailong Zhang 6,  Jianxiu Yu 7
Affiliations

Affiliations

  • 1 Department of Biochemistry and Molecular Cell Biology & Department of Thoracic Surgery Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
  • 2 School of Medicine, Shenzhen Campus of Sun Yat-sen University, Sun Yat-sen University, Shenzhen, Guangdong, 518107, China.
  • 3 College of Letters & Science, University of California-Santa Barbara, Santa Barbara, CA, 93106, USA.
  • 4 Department of Biochemistry and Molecular Cell Biology & Department of Thoracic Surgery Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. richardjiejie@hotmail.com.
  • 5 Department of Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201999, China. mingxu.msu@gmail.com.
  • 6 School of Medicine, Shenzhen Campus of Sun Yat-sen University, Sun Yat-sen University, Shenzhen, Guangdong, 518107, China. zhanghlong5@mail.sysu.edu.cn.
  • 7 Department of Biochemistry and Molecular Cell Biology & Department of Thoracic Surgery Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. Jianxiu.Yu@gmail.com.
  • # Contributed equally.
PMID: 40774970 DOI: 10.1038/s41467-025-62619-8
Abstract

Stress granules (SGs) are cytoplasmic, membraneless organelles that modulate mRNA metabolism and cellular adaptation under stress, yet the mechanisms by which they regulate Cancer cell survival remain unclear. Here, we identify Poly(A)-Binding Protein Cytoplasmic 1 (PABPC1), a core SG component, as stress-inducible SUMOylation target. Upon various stress conditions, SUMOylated PABPC1 promotes SG assembly and enhances Cancer cell survival. Transcriptome-wide analysis reveals that SUMOylated PABPC1 selectively stabilizes mRNAs enriched in conserved U-rich elements. Mechanistically, SUMOylated PABPC1 interacts with RNA-binding protein TIA1 to form PABPC1-SUMO-TIA1 complex that recruits U-rich mRNAs into SGs, protecting them from degradation. This process facilitates the expression of U-rich genes, such as mitophagy-related genes FUNDC1, BNIP3L, thereby maintaining cellular homeostasis and promoting cell survival under adverse conditions. Our findings reveal that PABPC1 SUMOylation connects stress granule assembly with selective U-rich mRNA stabilization and Mitophagy, promoting Cancer cell stress adaptation.

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