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

Taehee Kang, Nam Hoon Kwon, Jin Young Lee, Min Chul Park, Eunji Kang, Hyo Hyun Kim, Taek Jin Kang, Sunghoon Kim

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)

Abstract

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 (tRNAi 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 iMet in vitro, while it showed little or reduced interaction with unacylated or lysine-charged tRNAiMet. In addition, AIMP3 discriminates Met-tRNAiMet 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-tRNAiMet for the delivery of Met-tRNAiMet to ribosome. AIMP3 recruited active eIF2γ to the MRS-AIMP3 complex, and the level of Met-tRNAi 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-tRNAiMet transfer from MRS to eIF2 complex for the accurate and efficient translation initiation.

Original languageEnglish
Pages (from-to)475-481
Number of pages7
JournalJournal of Molecular Biology
Volume423
Issue number4
DOIs
Publication statusPublished - 2012 Nov

Bibliographical note

Funding Information:
This work was supported by the Global Frontier Project grant NRF-M1AXA002-2011-0028417 and National Research Foundation grants NRF-2011-0005849 and NRF-2011-0028394 funded by the Ministry of Education, Science and Technology of Korea .

All Science Journal Classification (ASJC) codes

  • Structural Biology
  • Molecular Biology

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