Co-regulation of mRNA translation by TDP-43 and Fragile X Syndrome protein FMRP.

摘要: For proper mammalian brain development and functioning, the translation of many neuronal mRNAs needs to be repressed without activity stimulations. We have discovered that expression a subclass proteins essential for neurodevelopment neuron plasticity is co-regulated at translational level by TDP-43 Fragile X Syndrome protein FMRP. Using molecular, cellular imaging approaches, we show these two RNA-binding (RBP) co-repress initiation Rac1, Map1b GluR1 mRNAs, consequently hippocampal spinogenesis. The co-repression occurs through binding mRNA(s) specific UG/GU sequences recruitment inhibitory CYFIP1-FMRP complex its glycine-rich domain. This novel regulatory scenario could utilized silence significant portion around 160 common target RBPs. study establishes functional/physical partnership between FMRP mechanistically links several neurodevelopmental disorders neurodegenerative diseases.