AIMP3/p18 controls translational initiation by mediating the delivery of charged initiator tRNA to initiation complex.

Aminoacyl-tRNA synthetase-interacting multifunctional proteins (AIMPs) are nonenzymatic scaffolding proteins that comprise multisynthetase complex (MSC) with nine aminoacyl-tRNA synthetases in higher eukaryotes. Among the three AIMPs, AIMP3/p18 is strongly anchored to methionyl-tRNA synthetase (MRS) in the MSC. MRS attaches methionine (Met) to initiator tRNA (tRNA(i)(Met)) and plays an important role in translation initiation. It is known that AIMP3 is dispatched to nucleus or nuclear membrane to induce DNA damage response or senescence; however, the role of AIMP3 in translation as a component of MSC and the meaning of its interaction with MRS are still unclear. Herein, we observed that AIMP3 specifically interacted with Met-tRNA(i)(Met)in vitro, while it showed little or reduced interaction with unacylated or lysine-charged tRNA(i)(Met). In addition, AIMP3 discriminates Met-tRNA(i)(Met) from Met-charged elongator tRNA based on filter-binding assay. Pull-down assay revealed that AIMP3 and MRS had noncompetitive interaction with eukaryotic initiation factor 2 (eIF2) γ subunit (eIF2γ), which is in charge of binding with Met-tRNA(i)(Met) for the delivery of Met-tRNA(i)(Met) to ribosome. AIMP3 recruited active eIF2γ to the MRS-AIMP3 complex, and the level of Met-tRNA(i)(Met) bound to eIF2 complex was reduced by AIMP3 knockdown resulting in reduced protein synthesis. All these results suggested the novel function of AIMP3 as a critical mediator of Met-tRNA(i)(Met) transfer from MRS to eIF2 complex for the accurate and efficient translation initiation. Copyright © 2012 Elsevier Ltd. All rights reserved.

Citation

Taehee Kang, Nam Hoon Kwon, Jin Young Lee, Min Chul Park, Eunji Kang, Hyo Hyun Kim, Taek Jin Kang, Sunghoon Kim. AIMP3/p18 controls translational initiation by mediating the delivery of charged initiator tRNA to initiation complex. Journal of molecular biology. 2012 Nov 2;423(4):475-81

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PMID: 22867704

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