Nuclear accumulation of mRNAs underlies G4C2 repeat-induced translational repression in a cellular model of C9orf72 ALS

• DOI: 10.1242/jcs.165332
• Publication Date: 2015-03-19T02:08:53Z
• Authors: Simona Rossi; Alessia Serrano; Valeria Gerbino; Alessandra Giorgi; Laura Di Francesco; Monica Nencini; Francesca Bozzo; Maria Eugenia Sch...; Claudia Bagni; Gianluca Cestra; Maria Teresa Carrì; Tilmann Achsel; Mauro Cozzolino
• Keywords: C9ORF72; Stress granule

A common feature of non-coding repeat expansion disorders is the accumulation RNA repeats as foci in nucleus and/or cytoplasm affected cells. These can be toxic by sequestering RNA-binding proteins, thus affecting various steps post-transcriptional gene regulation. However, precise step that C9orf72 GGGGCC (G4C2) expansion, major genetic cause Amyotrophic Lateral Sclerosis, still poorly defined. In this work, we set out to characterise these mechanisms identifying binding proteins. Sequestration some factors into was observed when a (G4C2)31 expressed NSC34 and HeLa Most notably, widely distribution Pur-alpha its partner FMRP, which accumulate intra-cytosolic granules are positive for stress markers. Accordingly, translational repression induced. Interestingly, effect associated marked poly(A) mRNAs cell nuclei. Thus, defective trafficking mRNA, consequence impaired nuclear mRNA export, might affect translation efficiency contribute pathogenesis ALS.