Multifunctional polyribosome-associated RNA-binding proteinthat plays a central role in neuronal development and synapticplasticity through the regulation of alternative mRNA splicing, mRNAstability, mRNA dendritic transport and postsynaptic local proteinsynthesis of a subset of mRNAs. Plays a role in thealternative splicing of its own mRNA. Plays a role inmRNA nuclear export. Together with export factor NXF2, is involved in the regulation of the NXF1 mRNA stability in neurons. Stabilizes the scaffolding postsynaptic density proteinDLG4/PSD-95 and the myelin basic protein (MBP) mRNAs in hippocampalneurons and glial cells, respectively; this stabilization is furtherincreased in response to metabotropic glutamate receptor (mGluR) stimulation. Plays a role in selective delivery of asubset of dendritic mRNAs to synaptic sites in response to mGluRactivation in a kinesin-dependent manner. Plays a roleas a repressor of mRNA translation during the transport of dendriticmRNAs to postsynaptic dendritic spines. Component of theCYFIP1-EIF4E-FMR1 complex which blocks cap-dependent mRNA translationinitiation. Represses mRNA translation by stallingribosomal translocation during elongation. Reports arecontradictory with regards to its ability to mediate translationinhibition of MBP mRNA in oligodendrocytes. Alsoinvolved in the recruitment of the RNA helicase MOV10 to a subset ofmRNAs and hence regulates microRNA (miRNA) -mediated translationalrepression by AGO2. Facilitates the assembly of miRNAs on specific target mRNAs. Plays also a role as an activator of mRNAtranslation of a subset of dendritic mRNAs at synapses. In response to mGluR stimulation, FMR1-target mRNAs are rapidly derepressed, allowing for localtranslation at synapses. Binds to a large subset ofdendritic mRNAs that encode a myriad of proteins involved in pre- andpostsynaptic functions. Binds to 5'-ACU[GU]-3' and/or 5'-[AU]GGA-3' RNAconsensus sequences within mRNA targets, mainly at coding sequence (CDS) and 3'-untranslated region (UTR) and less frequently at 5'-UTR. Binds to intramolecular G-quadruplex structures inthe 5'- or 3'-UTRs of mRNA targets. Binds to G-quadruplex structures inthe 3'-UTR of its own mRNA. Binds also to RNAligands harboring a kissing complex (kc) structure; this binding maymediate the association of FMR1 with polyribosomes. Binds mRNAs containing U-rich target sequences. Bindsto a triple stem-loop RNA structure, called Sod1 stem loop interactingwith FMRP (SoSLIP), in the 5'-UTR region of superoxide dismutase SOD1mRNA. Binds to the dendritic, small non-coding braincytoplasmic RNA 1 (BC1); which may increase the association of theCYFIP1-EIF4E-FMR1 complex to FMR1 target mRNAs at synapses. Associates with export factor NXF1 mRNA-containingribonucleoprotein particles (mRNPs) in a NXF2-dependent manner. Binds to a subset of miRNAs in the brain. May associate with nascent transcripts in a nuclearprotein NXF1-dependent manner. In vitro, binds to RNAhomomer; preferentially on poly (G) and to a lesser extent on poly (U), but not on poly (A) or poly (C). Moreover, plays arole in the modulation of the sodium-activated potassium channel KCNT1gating activity. Negatively regulates the voltage-dependent calcium channel current density in soma and presynapticterminals of dorsal root ganglion (DRG) neurons, and hence regulatessynaptic vesicle exocytosis. Modulates the voltage-dependent calcium channel CACNA1B expression at the plasma membrane bytargeting the channels for proteosomal degradation. Plays a role in regulation of MAP1B-dependent microtubule dynamicsduring neuronal development. Recently, has been shownto play a translation-independent role in the modulation of presynapticaction potential (AP) duration and neurotransmitter release via large-conductance calcium-activated potassium (BK) channels in hippocampaland cortical excitatory neurons. Finally, FMR1 may beinvolved in the control of DNA damage response (DDR) mechanisms throughthe regulation of ATR-dependent signaling pathways such as histoneH2AX/H2A. x and BRCA1 phosphorylations. [1-6]

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