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

Cell
Xiaoju Max MaJohn Blenis

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.

References

Feb 20, 1992·Nature·S Piñol-Roma, G Dreyfuss
Jan 15, 1991·Proceedings of the National Academy of Sciences of the United States of America·R D PalmiterR L Brinster
Dec 1, 1987·Genes & Development·J CallisV Walbot
Jun 29, 2000·Annual Review of Biochemistry·A C GingrasN Sonenberg
Apr 12, 2001·Genes & Development·A C GingrasN Sonenberg
Jul 18, 2002·Current Biology : CB·Josée Dostie, Gideon Dreyfuss
Sep 13, 2002·Nature·Zhaolan ZhouRobin Reed
Apr 26, 2003·Trends in Biochemical Sciences·Hervé Le HirMelissa J Moore
Sep 16, 2003·Proceedings of the National Academy of Sciences of the United States of America·Heather L WiegandBryan R Cullen
Mar 23, 2004·Nature Structural & Molecular Biology·Toshiharu ShibuyaMelissa J Moore
May 18, 2004·Current Opinion in Cell Biology·Thomas Ø TangeMelissa J Moore
Aug 18, 2004·Genes & Development·Nissim Hay, Nahum Sonenberg
Sep 3, 2004·Current Biology : CB·Celeste J RichardsonJohn Blenis
Sep 14, 2004·Nature Structural & Molecular Biology·Fabrice LejeuneLynne E Maquat
Mar 1, 2005·Trends in Genetics : TIG·Miles F Wilkinson
May 20, 2005·Current Opinion in Cell Biology·Robin Reed, Hong Cheng
May 20, 2005·Current Opinion in Cell Biology·Fabrice Lejeune, Lynne E Maquat
Aug 24, 2005·Nature Structural & Molecular Biology·Jayanthi P GudikoteMiles F Wilkinson
Dec 28, 2006·Cell·Hong ChengRobin Reed
Mar 14, 2007·Annual Review of Biochemistry·Yao-Fu ChangMiles F Wilkinson

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Citations

Nov 17, 2010·Chromosoma·Petra Björk, Lars Wieslander
Oct 5, 2013·Trends in Genetics : TIG·Bijoyita Roy, Allan Jacobson
Oct 30, 2013·Nature Neuroscience·Mauro Costa-Mattioli, Lisa M Monteggia
Mar 7, 2012·Nature Reviews. Genetics·Daniel R Schoenberg, Lynne E Maquat
Apr 3, 2009·Nature Reviews. Molecular Cell Biology·Xiaoju Max Ma, John Blenis
Dec 16, 2010·Nature Reviews. Molecular Cell Biology·Roberto ZoncuDavid M Sabatini
Feb 5, 2009·Nature Structural & Molecular Biology·Saverio Brogna, Jikai Wen
Dec 6, 2012·Nature Structural & Molecular Biology·Oliver Mühlemann
Mar 27, 2013·Proceedings of the National Academy of Sciences of the United States of America·Pierre-Etienne ChazalHervé Le Hir
Aug 17, 2012·Hybridoma·Lilia SavinskaValeriy Filonenko
Mar 16, 2012·Molecular Biology of the Cell·Elisabeth DaguenetCatherine Tomasetto
Jan 20, 2010·The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences·Zelton Dave Sharp, Randy Strong
Dec 9, 2010·Journal of Molecular Cell Biology·Xuemin Wang, Christopher G Proud
Jul 17, 2008·Nucleic Acids Research·Chung-Sheng LeeRobin Reed
Nov 29, 2011·Nucleic Acids Research·Fabienne C FieselPhilipp J Kahle
Apr 30, 2010·Journal of Virology·Chad M SwansonMichael H Malim
Oct 11, 2008·The Journal of Clinical Investigation·Samira AlliouacheneMario Pende
Mar 13, 2010·Genome Biology·Can CenikFrederick P Roth
May 1, 2013·PLoS Biology·Kohila MahadevanAlexander F Palazzo
Nov 22, 2011·PLoS Computational Biology·Joshua LequieuJeffrey D Varner
Mar 19, 2013·PloS One·Mustapha KandouzGerald Batist
Apr 7, 2011·Experimental & Molecular Medicine·Chang Hoon Cho
Jul 1, 2008·Regenerative Medicine·Amit N Patel, Francisco Silva
Nov 13, 2013·Proceedings of the National Academy of Sciences of the United States of America·Donald S KirkpatrickKlaus P Hoeflich
Mar 29, 2014·The Journal of Endocrinology·Philip NewsholmeKevin Keane

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