The exon-junction-complex-component metastatic lymph node 51 functions in stress-granule assembly.
Metastatic lymph node 51 [MLN51 (also known as CASC3)] is a component of the exon junction complex (EJC), which is assembled on spliced mRNAs and plays important roles in post-splicing events. The four proteins of the EJC core, MLN51, MAGOH, Y14 and EIF4AIII shuttle between the cytoplasm and the nucleus. However, unlike the last three, MLN51 is mainly detected in the cytoplasm, suggesting that it plays an additional function in this compartment. In the present study, we show that MLN51 is recruited into cytoplasmic aggregates known as stress granules (SGs) together with the SG-resident proteins, fragile X mental retardation protein (FMRP), poly(A) binding protein (PABP) and poly(A)(+) RNA. MLN51 specifically associates with SGs via its C-terminal region, which is dispensable for its incorporation in the EJC. MLN51 does not promote SG formation but its silencing, or the overexpression of a mutant lacking its C-terminal region, alters SG assembly. Finally, in human breast carcinomas, MLN51 is sometimes present in cytoplasmic foci also positive for FMRP and PABP, suggesting that SGs formation occurs in malignant tumours.
Baguet
Aurélie
A
Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Département de Biologie du Cancer, UMR 7104 CNRS/U596 INSERM/Université Louis Pasteur, BP 10142, 67404 Illkirch, C.U. de Strasbourg, France.
Degot
Sébastien
S
Cougot
Nicolas
N
Bertrand
Edouard
E
Chenard
Marie-Pierre
MP
Wendling
Corinne
C
Kessler
Pascal
P
Le Hir
Hervé
H
Rio
Marie-Christine
MC
Tomasetto
Catherine
C
D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology; D002470:Cell Survival; D003594:Cytoplasmic Granules / Q000378:metabolism*; D015536:Down-Regulation / Q000235:genetics; D020717:Eukaryotic Initiation Factor-2B / Q000378:metabolism; D005091:Exons / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D006801:Humans; D021962:Membrane Microdomains / Q000378:metabolism; D009363:Neoplasm Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D021381:Protein Transport; D016601:RNA-Binding Proteins; D015854:Up-Regulation / Q000235:genetics
C459802:CASC3 protein, human; D020717:Eukaryotic Initiation Factor-2B; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins