SKAR links pre-mRNA splicing to mTOR/S6K1-mediated enhanced translation efficiency of spliced mRNAs.
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.
Ma
Xiaoju Max
XM
Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA.
Yoon
Sang-Oh
SO
Richardson
Celeste J
CJ
Jülich
Kristina
K
Blenis
John
J
D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D039601:Eukaryotic Initiation Factor-4A / Q000378:metabolism; D005091:Exons; D006801:Humans; D039502:Nuclear Cap-Binding Protein Complex / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism*; D014176:Protein Biosynthesis; D011494:Protein Kinases / Q000378:metabolism*; D012326:RNA Splicing; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D012261:Ribonucleoproteins / Q000378:metabolism; D019893:Ribosomal Protein S6 Kinases / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases
D039502:Nuclear Cap-Binding Protein Complex; D009687:Nuclear Proteins; C495327:POLDIP3 protein, human; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins; C026452:messenger ribonucleoprotein; D011494:Protein Kinases; C546842:MTOR protein, human; D019893:Ribosomal Protein S6 Kinases; D058570:TOR Serine-Threonine Kinases; D039601:Eukaryotic Initiation Factor-4A