Gene interactions and pathways from curated databases and text-mining
Cell 2008, PMID: 18423201

SKAR links pre-mRNA splicing to mTOR/S6K1-mediated enhanced translation efficiency of spliced mRNAs.

Ma, Xiaoju Max; Yoon, Sang-Oh; Richardson, Celeste J; J├╝lich, Kristina; Blenis, John

Different protein complexes form on newly spliced mRNA to ensure the accuracy and efficiency of eukaryotic gene expression. For example, the exon junction complex (EJC) plays an important role in mRNA surveillance. The EJC also influences the first, or pioneer round of protein synthesis through a mechanism that is poorly understood. We show that the nutrient-, stress-, and energy-sensing checkpoint kinase, mTOR, contributes to the observed enhanced translation efficiency of spliced over nonspliced mRNAs. We demonstrate that, when activated, S6K1 is recruited to the newly synthesized mRNA by SKAR, which is deposited at the EJC during splicing, and that SKAR and S6K1 increase the translation efficiency of spliced mRNA. Thus, SKAR-mediated recruitment of activated S6K1 to newly processed mRNPs serves as a conduit between mTOR checkpoint signaling and the pioneer round of translation when cells exist in conditions supportive of protein synthesis.

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Text Mining Data

S6K1 → SKAR: " We demonstrate that, when activated, S6K1 is recruited to the newly synthesized mRNA by SKAR, which is deposited at the EJC during splicing, and that SKAR and S6K1 increase the translation efficiency of spliced mRNA "

Manually curated Databases

  • IRef Intact Interaction: Complex of EIF3B-NCBP1-RPS6KB1-EIF3B-EIF4E-RPS6KB1-NCBP1-EIF4E (association, anti bait coimmunoprecipitation)
  • IRef Intact Interaction: Complex of RPS6KB1-EIF3B-NCBP1-MTOR-EIF3B-MTOR-NCBP1-RPS6KB1 (association, anti tag coimmunoprecipitation)
  • IRef Intact Interaction: POLDIP3 — NCBP1 (physical association, anti bait coimmunoprecipitation)
  • IRef Intact Interaction: NCBP1 — RPS6 (physical association, anti bait coimmunoprecipitation)
  • IRef Intact Interaction: NCBP1 — RPS6 (physical association, anti tag coimmunoprecipitation)
  • IRef Intact Interaction: Complex of RPS6-EIF4E-RPS6KB1 (association, anti bait coimmunoprecipitation)
  • IRef Intact Interaction: Complex of RPS6-RPS6KB1-EIF3B-NCBP1 (association, anti tag coimmunoprecipitation)
  • IRef Intact Interaction: Complex of EIF4A3-POLDIP3-NCBP1 (association, anti bait coimmunoprecipitation)
  • IRef Intact Interaction: SRSF2 — POLDIP3 (colocalization, fluorescence microscopy)
  • IRef Intact Interaction: Complex of NCBP1-EIF3B-EIF3B-RPS6KB1-NCBP1-RPS6KB1 (association, anti tag coimmunoprecipitation)
  • IRef Intact Interaction: Complex of 13 proteins (association, anti bait coimmunoprecipitation)
  • IRef Intact Interaction: Complex of NCBP1-EIF3B-MTOR-EIF4E (association, anti bait coimmunoprecipitation)
  • IRef Intact Interaction: Complex of UPF3B-POLDIP3-NCBP1 (association, anti tag coimmunoprecipitation)
  • NCI Pathway Database mTOR signaling pathway: SKAR/EJC/mRNA cap binding complex/p70S6K complex (POLDIP3-RPS6KB1) → SKAR/EJC/mRNA cap binding complex complex (POLDIP3) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database mTOR signaling pathway: SKAR/EJC/mRNA cap binding complex/p70S6K complex (POLDIP3-RPS6KB1) → p70S6K (RPS6KB1) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database mTOR signaling pathway: SKAR/EJC/mRNA cap binding complex complex (POLDIP3) → p70S6K (RPS6KB1) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction
In total, 23 gene pairs are associated to this article in curated databases