Cells Lacking the Fragile X Mental Retardation Protein (FMRP) have Normal RISC Activity but Exhibit Altered Stress Granule Assembly

被引:73
作者
Didiot, Marie-Cecile
Subramanian, Murugan
Flatter, Eric
Mandel, Jean-Louis
Moine, Herve [1 ]
机构
[1] IGBMC, F-67404 Illkirch Graffenstaden, France
基金
美国国家卫生研究院;
关键词
MESSENGER-RNA; TRANSLATING POLYRIBOSOMES; PROCESSING BODIES; P-BODIES; BC1; RNA; MICRORNA; LOCALIZATION; TIA-1; INTERFERENCE; MECHANISMS;
D O I
10.1091/mbc.E08-07-0737
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The fragile X mental retardation protein (FMRP) is an RNA-binding protein involved in the mRNA metabolism. The absence of FMRP in neurons leads to alterations of the synaptic plasticity, probably as a result of translation regulation defects. The exact molecular mechanisms by which FMRP plays a role in translation regulation have remained elusive. The finding of an interaction between FMRP and the RNA interference silencing complex (RISC), a master of translation regulation, has suggested that both regulators could be functionally linked. We investigated here this link, and we show that FMRP exhibits little overlap both physically and functionally with the RISC machinery, excluding a direct impact of FMRP on RISC function. Our data indicate that FMRP and RISC are associated to distinct pools of mRNAs. FMRP, unlike RISC machinery, associates with the pool of mRNAs that eventually goes into stress granules upon cellular stress. Furthermore, we show that FMRP plays a positive role in this process as the lack of FMRP or a point mutant causing a severe fragile X alter stress granule formation. Our data support the proposal that FMRP plays a role in controlling the fate of mRNAs after translation arrest.
引用
收藏
页码:428 / 437
页数:10
相关论文
共 53 条
[1]  
Anderson P, 2002, J CELL SCI, V115, P3227
[2]   RNA granules [J].
Anderson, P ;
Kedersha, N .
JOURNAL OF CELL BIOLOGY, 2006, 172 (06) :803-808
[3]   The fragile X mental retardation protein and group I metabotropic glutamate receptors regulate levels of mRNA granules in brain [J].
Aschrafi, A ;
Cunningham, BA ;
Edelman, GM ;
Vanderklish, PW .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (06) :2180-2185
[4]   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
[5]   Staufen- and FMRP-containing neuronal RNPs are structurally and functionally related to somatic P bodies [J].
Barbee, Scott A. ;
Estes, Patricia S. ;
Cziko, Anne-Marie ;
Hillebrand, Jens ;
Luedeman, Rene A. ;
Coller, Jeff M. ;
Johnson, Nick ;
Howlett, Iris C. ;
Geng, Cuiyun ;
Ueda, Ryu ;
Brand, Andrea H. ;
Newbury, Sarah F. ;
Wilhelm, James E. ;
Levine, Richard B. ;
Nakamura, Akira ;
Parker, Roy ;
Ramaswami, Mani .
NEURON, 2006, 52 (06) :997-1009
[6]   A guided tour into subcellular colocalization analysis in light microscopy [J].
Bolte, S. ;
Cordelieres, F. P. .
JOURNAL OF MICROSCOPY, 2006, 224 (213-232) :213-232
[7]   FMRP interferes with the Rac1 pathway and controls actin cytoskeleton dynamics in murine fibroblasts [J].
Castets, M ;
Schaeffer, C ;
Bechara, E ;
Schenck, A ;
Khandjian, EW ;
Luche, S ;
Moine, H ;
Rabilloud, T ;
Mandel, JL ;
Bardoni, B .
HUMAN MOLECULAR GENETICS, 2005, 14 (06) :835-844
[8]   Fragile X-related protein and VIG associate with the RNA interference machinery [J].
Caudy, AA ;
Myers, M ;
Hannon, GJ ;
Hammond, SM .
GENES & DEVELOPMENT, 2002, 16 (19) :2491-2496
[9]   GERp95, a membrane-associated protein that belongs to a family of proteins involved in stem cell differentiation [J].
Cikaluk, DE ;
Tahbaz, N ;
Hendricks, LC ;
DiMattia, GE ;
Hansen, D ;
Pilgrim, D ;
Hobman, TC .
MOLECULAR BIOLOGY OF THE CELL, 1999, 10 (10) :3357-3372
[10]   The fragile X mental retardation protein is associated with poly(A)(+) mRNA in actively translating polyribosomes [J].
Corbin, F ;
Bouillon, M ;
Fortin, A ;
Morin, S ;
Rousseau, F ;
Khandjian, EW .
HUMAN MOLECULAR GENETICS, 1997, 6 (09) :1465-1472