SUMO-2 promotes mRNA translation by enhancing interaction between eIF4E and eIF4G.

Li-Zhao Chen,Zhi-Ya Sun,An-Xiong Luo,Wei Xing,Xiang-Yun Li,Jing He,Hua-Ping Liang,Wei Guo,Hong Huang,Jing Hu,Yun-Sheng Xu,Xiang Xu,Zheng-Guo Wang,Yoon Ki Kim

doi:10.1371/journal.pone.0100457

Abstract

Small ubiquitin-like modifier (SUMO) proteins regulate many important eukaryotic cellular processes through reversible covalent conjugation to target proteins. In addition to its many well-known biological consequences, like subcellular translocation of protein, subnuclear structure formation, and modulation of transcriptional activity, we show here that SUMO-2 also plays a role in mRNA translation. SUMO-2 promoted formation of the active eukaryotic initiation factor 4F (eIF4F) complex by enhancing interaction between Eukaryotic Initiation Factor 4E (eIF4E) and Eukaryotic Initiation Factor 4G (eIF4G), and induced translation of a subset of proteins, such as cyclinD1 and c-myc, which essential for cell proliferation and apoptosis. As expected, overexpression of SUMO-2 can partially cancel out the disrupting effect of 4EGI-1, a small molecule inhibitor of eIF4E/eIF4G interaction, on formation of the eIF4F complex, translation of the cap-dependent protein, cell proliferation and apoptosis. On the other hand, SUMO-2 knockdown via shRNA partially impaired cap-dependent translation and cell proliferation and promoted apoptosis. These results collectively suggest that SUMO-2 conjugation plays a crucial regulatory role in protein synthesis. Thus, this report might contribute to the basic understanding of mammalian protein translation and sheds some new light on the role of SUMO in this process.

Highlights

Small ubiquitin-like modifiers (SUMO) are ubiquitin-related proteins that can be covalently conjugated to target proteins in cells to modify their function
Both SUMO-1 and Ubc9 can promote protein translation, and we suspected that SUMO-2 or SUMO-3 may play a part in mRNA translation
We provided evidences to show that SUMO-2 can promote cap-dependent protein translation, while SUMO-3 seems to be involved in IRES

Summary

Introduction

Small ubiquitin-like modifiers (SUMO) are ubiquitin-related proteins that can be covalently conjugated to target proteins in cells to modify their function. Four SUMO isoforms encoded by separate genes, designated SUMO-1 to SUMO-4, have been identified in humans [1,2]. The sequence identity and expression of these four SUMO molecules is highly variable. Protein sumoylation is mediated by activating (E1), conjugating (E2) and ligating (E3) enzymes [6]. Ubc is the only identified SUMO E2 conjugating enzyme, which is sufficient for sumoylation. The E3 ligase promotes the efficiency of sumoylation and in some cases has been shown to direct SUMO conjugation onto non-consensus motifs [7]. Sumoylation is reversible and is removed from targets by several specific SUMO proteases in an ATP-dependent manner [8]

Methods

Results

Conclusion