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PMID:18423201

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Citation

Ma, XM, Yoon, SO, Richardson, CJ, Jülich, K and Blenis, J (2008) SKAR links pre-mRNA splicing to mTOR/S6K1-mediated enhanced translation efficiency of spliced mRNAs. Cell 133:303-13

Abstract

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.

Links

PubMed Online version:10.1016/j.cell.2008.02.031

Keywords

Cell Line; Cell Nucleus/metabolism; Cytoplasm/metabolism; Eukaryotic Initiation Factor-4A/metabolism; Exons; Humans; Nuclear Cap-Binding Protein Complex/metabolism; Nuclear Proteins/metabolism; Protein Biosynthesis; Protein Kinases/metabolism; RNA Splicing; RNA, Messenger/metabolism; RNA-Binding Proteins/metabolism; Ribonucleoproteins/metabolism; Ribosomal Protein S6 Kinases/metabolism; TOR Serine-Threonine Kinases

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:KS6B1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P55884

F

Seeded From UniProt

complete

HUMAN:IF4A3

involved_in

GO:0045727: positive regulation of translation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:IF4A3

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9BY77

F

Seeded From UniProt

complete

HUMAN:EIF3B

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P23443

F

Seeded From UniProt

complete

HUMAN:RS6

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q09161

F

Seeded From UniProt

complete

HUMAN:NCBP1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P62753

F

Seeded From UniProt

complete

HUMAN:NCBP1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9BY77

F

Seeded From UniProt

complete

HUMAN:PDIP3

located_in

GO:0005737: cytoplasm

ECO:0000304: author statement supported by traceable reference used in manual assertion

C

Seeded From UniProt

complete

HUMAN:PDIP3

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P38919

F

Seeded From UniProt

complete

HUMAN:PDIP3

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q09161

F

Seeded From UniProt

complete

HUMAN:PDIP3

located_in

GO:0016607: nuclear speck

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:PDIP3

involved_in

GO:0045727: positive regulation of translation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:PDIP3

enables

GO:0044877: protein-containing complex binding

ECO:0000353: physical interaction evidence used in manual assertion

ComplexPortal:CPX-1941

F

Seeded From UniProt

complete

HUMAN:KS6B1

involved_in

GO:0045727: positive regulation of translation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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