Overexpression of MLN51 triggers P-body disassembly and formation of a new type of RNA granules

被引:19
作者
Cougot, Nicolas [1 ]
Daguenet, Elisabeth [2 ]
Baguet, Aurelie [2 ]
Cavalier, Annie [1 ]
Thomas, Daniel [1 ]
Bellaud, Pascale
Fautrel, Alain [3 ]
Godey, Florence [3 ,4 ]
Bertrand, Edouard [5 ]
Tomasetto, Catherine [2 ]
Gillet, Reynald [1 ]
机构
[1] Univ Rennes 1, IGDR, Translat & Folding Team, UMR CNRS 6290, F-35042 Rennes, France
[2] Univ Strasbourg, CNRS, INSERM, Inst Genet & Biol Mol & Cellulaire,UMR 7104,U964, F-67404 Illkirch Graffenstaden, France
[3] Univ Rennes 1, GFAS, Unite INSERM 991, Plateforme Histopathol,IFR 140, F-35043 Rennes, France
[4] Ctr Eugene Marquis, Ctr Ressources Biol Sante Rennes, F-35042 Rennes, France
[5] CNRS, Inst Mol Genet Montpellier, UMR 5535, F-34293 Montpellier 5, France
关键词
Breast cancer; mRNA; MLN51; P-bodies; Stress granules; EXON-JUNCTION-COMPLEX; MESSENGER-RNA; BREAST-CANCER; PROCESSING BODIES; METASTATIC LYMPH-NODE-51; TRANSLATIONAL REPRESSION; MAMMALIAN-CELLS; STRESS GRANULES; CORE COMPLEX; DECAY;
D O I
10.1242/jcs.154500
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Metastatic lymph node 51 (MLN51, also known as CASC3) is a core component of the exon junction complex (EJC), which is loaded onto spliced mRNAs and plays an essential role in determining their fate. Unlike the three other EJC core components [eIF4AIII, Magoh and Y14 (also known as RBM8A)], MLN51 is mainly located in the cytoplasm, where it plays a key role in the assembly of stress granules. In this study, we further investigated the cytoplasmic role of MLN51. We show that MLN51 is a new component of processing bodies (P-bodies). When overexpressed, MLN51 localizes in novel small cytoplasmic foci. These contain RNA, show directed movements and are distinct from stress granules and P-bodies. The appearance of these foci correlates with the process of P-body disassembly. A similar reduction in P-body count is also observed in human HER2-positive (HER2(+)) breast cancer cells overexpressing MLN51. This suggests that P-body disassembly and subsequent mRNA deregulation might correlate with cancer progression.
引用
收藏
页码:4692 / 4701
页数:10
相关论文
共 43 条
[1]   The Dynamics of Mammalian P Body Transport, Assembly, and Disassembly In Vivo [J].
Aizer, Adva ;
Brody, Yehuda ;
Ler, Lian Wee ;
Sonenberg, Nahum ;
Singer, Robert H. ;
Shav-Tal, Yaron .
MOLECULAR BIOLOGY OF THE CELL, 2008, 19 (10) :4154-4166
[2]   Intracellular trafficking and dynamics of P bodies [J].
Aizer, Adva ;
Shav-Tal, Yaron .
PRION, 2008, 2 (04) :131-134
[3]   RNA granules [J].
Anderson, P ;
Kedersha, N .
JOURNAL OF CELL BIOLOGY, 2006, 172 (06) :803-808
[4]   A role for eIF4E and eIF4E-transporter in targeting mRNPs to mammalian processing bodies [J].
Andrei, MA ;
Ingelfinger, D ;
Heintzmann, R ;
Achsel, T ;
Rivera-Pomar, R ;
Lührmann, R .
RNA, 2005, 11 (05) :717-727
[5]   Genomic analysis of the HER2/TOP2A amplicon in breast cancer and breast cancer cell lines [J].
Arriola, Edurne ;
Marchio, Caterina ;
Tan, David Sp ;
Drury, Suzanne C. ;
Lambros, Maryou B. ;
Natrajan, Rachael ;
Rodriguez-Pinilla, Socorro Maria ;
Mackay, Alan ;
Tamber, Narinder ;
Fenwick, Kerry ;
Jones, Chris ;
Dowsett, Mitch ;
Ashworth, Alan ;
Reis-Filho, Jorge S. .
LABORATORY INVESTIGATION, 2008, 88 (05) :491-503
[6]   The exon-junction-complex-component metastatic lymph node 51 functions in stress-granule assembly [J].
Baguet, Aurelie ;
Degot, Sebastien ;
Cougot, Nicolas ;
Bertrand, Edouard ;
Chenard, Marie-Pierre ;
Wendling, Corinne ;
Kessler, Pascal ;
Le Hir, Herve ;
Rio, Marie-Christine ;
Tomasetto, Catherine .
JOURNAL OF CELL SCIENCE, 2007, 120 (16) :2774-2784
[7]   Polysomes, P bodies and stress granules: states and fates of eukaryotic mRNAs [J].
Balagopal, Vidya ;
Parker, Roy .
CURRENT OPINION IN CELL BIOLOGY, 2009, 21 (03) :403-408
[8]   The exon junction core complex is locked onto RNA by inhibition of eIF4AIII ATPase activity [J].
Ballut, L ;
Marchadier, B ;
Baguet, A ;
Tomasetto, C ;
Séraphin, B ;
Le Hir, H .
NATURE STRUCTURAL & MOLECULAR BIOLOGY, 2005, 12 (10) :861-869
[9]  
Bieche I, 1996, CANCER RES, V56, P3886
[10]   Eukaryotic Stress Granules: The Ins and Outs of Translation [J].
Buchan, J. Ross ;
Parker, Roy .
MOLECULAR CELL, 2009, 36 (06) :932-941