FEATURES

FAMILY

DESCRIPTION

Also known as FMR1_MOUSE, Fmr1, Fmr-1. Multifunctional polyribosome-associated RNA-binding protein that plays a central role in neuronal development and synaptic plasticity through the regulation of alternative mRNA splicing, mRNA stability, mRNA dendritic transport and postsynaptic local protein synthesis of a subset of mRNAs (PubMed:11438589, PubMed:12032354, PubMed:15475576, PubMed:16631377, PubMed:16790844, PubMed:17417632, PubMed:17548835, PubMed:18539120, PubMed:18653529, PubMed:19640847, PubMed:19166269, PubMed:20159450, PubMed:21784246, PubMed:23235829, PubMed:24813610). Plays a role in the alternative splicing of its own mRNA (PubMed:18653529). Plays a role in mRNA nuclear export (PubMed:16790844). Together with export factor NXF2, is involved in the regulation of the NXF1 mRNA stability in neurons (PubMed:17548835). Stabilizes the scaffolding postsynaptic density protein DLG4/PSD-95 and the myelin basic protein MBP mRNAs in hippocampal neurons and glial cells, respectively; this stabilization is further increased in response to metabotropic glutamate receptor (mGluR) stimulation (PubMed:17417632). Plays a role in selective delivery of a subset of dendritic mRNAs to synaptic sites in response to mGluR activation in a kinesin-dependent manner (PubMed:18539120). Plays a role as a repressor of mRNA translation during the transport of dendritic mRNAs to postsynaptic dendritic spines (PubMed:11376146, PubMed:12581522, PubMed:14570712, PubMed:12927206, PubMed:15475576, PubMed:16908410, PubMed:18805096, PubMed:19640847, PubMed:21784246, PubMed:23235829). Component of the CYFIP1-EIF4E-FMR1 complex which blocks cap-dependent mRNA translation initiation (PubMed:18805096). Represses mRNA translation by stalling ribosomal translocation during elongation (PubMed:21784246). Reports are contradictory with regards to its ability to mediate translation inhibition of (MBP) mRNA in oligodendrocytes (PubMed:14613971, PubMed:23891804). Also involved in the recruitment of the RNA helicase MOV10 to a subset of mRNAs and hence regulates microRNA (miRNA)-mediated translational repression by AGO2 (PubMed:20159450, PubMed:25464849). Facilitates the assembly of miRNAs on specific target mRNAs (By similarity). Plays also a role as an activator of mRNA translation of a subset of dendritic mRNAs at synapses (PubMed:14614133, PubMed:14613971, PubMed:15548614, PubMed:19640847, PubMed:19166269, PubMed:21490210). In response to mGluR stimulation, FMR1-target mRNAs are rapidly derepressed, allowing for local translation at synapses (PubMed:16908410, PubMed:17507556, PubMed:19640847). Binds to a large subset of dendritic mRNAs that encode a myriad of proteins involved in pre- and postsynaptic functions (PubMed:11719188, PubMed:11376146, PubMed:14613971, PubMed:17507556, PubMed:21784246, PubMed:21490210, PubMed:24349419). Binds to 5'-ACU[GU]-3' and/or 5'-[AU]GGA-3' RNA consensus sequences within mRNA targets, mainly at coding sequence (CDS) and 3'-untranslated region (UTR) and less frequently at 5'-UTR (By similarity). Binds to intramolecular G-quadruplex structures in the 5'- or 3'-UTRs of mRNA targets (PubMed:25692235). Binds to G-quadruplex structures in the 3'-UTR of its own mRNA (By similarity). Binds also to RNA ligands harboring a kissing complex (kc) structure; this binding may mediate the association of FMR1 with polyribosomes (By similarity). Binds mRNAs containing U-rich target sequences (By similarity). Binds to a triple stem-loop RNA structure, called Sod1 stem loop interacting with FMRP (SoSLIP), in the 5'-UTR region of superoxide dismutase SOD1 mRNA (PubMed:19166269). Binds to the dendritic, small non-coding brain cytoplasmic RNA 1 (BC1); which may increase the association of the CYFIP1-EIF4E-FMR1 complex to FMR1 target mRNAs at synapses (PubMed:12581522, PubMed:18805096). Associates with export factor NXF1 mRNA-containing ribonucleoprotein particles (mRNPs) in a NXF2-dependent manner (PubMed:17548835). Binds to a subset of miRNAs in the brain (PubMed:20159450). May associate wi Homodimer (By similarity). Forms heterodimer with FXR1; heterodimerization occurs in a methylation-dependent manner (By similarity). Forms heterodimer with FXR2 (By similarity). Homooligomer (By similarity). Component of the CYFIP1-EIF4E-FMR1 complex at least composed of CYFIP, EIF4E and FMR1; this mRNA cap binding complex formation increases in presence of the brain cytoplasmic RNA BC1 and is dynamically regulated in an activity-dependent manner to repress and then possibly release dendritic mRNAs for translation in response to mGluR stimulation (PubMed:18805096). Associates with the SMN core complex that contains SMN, GEMIN2/SIP1, DDX20/GEMIN3, GEMIN4, GEMIN5, GEMIN6, GEMIN7, GEMIN8 and STRAP/UNRIP (PubMed:18093976). Part of a ribonucleoprotein complex with AGO2/EIF2C2 and miRNAs (By similarity). Interacts with AGO2/EIF2C2 (By similarity). Interacts (via C-terminus) with CACNA1B; this interaction induces a decrease in the number of presynaptic functional CACNA1B channels at the cell surface (PubMed:24709664). Interacts with CYFIP1; this interaction recruits CYFIP1 to capped mRNA (PubMed:11438699, PubMed:18805096). Interacts with CYFIP2 (PubMed:11438699). Interacts with EIF5; this interaction occurs in a RNA-dependent manner (By similarity). Interacts with dynein (PubMed:18539120). Interacts with FXR1 and FXR2 (PubMed:10567518). Interacts with methylated histone H3 (By similarity). Interacts with IGF2BP1; this interaction allows to recruit IGF2BP1 to mRNA in a FMR1-dependent manner (By similarity). Interacts (via N-terminus) with KCNMB4 (PubMed:25561520). Interacts with KCNT1 (via C-terminus); this interaction alters gating properties of KCNT1 (PubMed:20512134). Interacts (via C-terminus) with KIF5A; this interaction is increased in a mGluR-dependent manner (PubMed:18539120). Interacts (via phosphorylated form) with MCRS1 (via N-terminus) (By similarity). Interacts with MOV10; this interaction is direct, occurs in an RNA-dependent manner on polysomes and induces association of MOV10 with RNAs (PubMed:25464849). Interacts with MYO5A and PURA; these interactions occur in association with polyribosome (PubMed:12147688). Interacts with NCL (PubMed:10567518). Interacts with NUFIP1 (PubMed:10556305). Interacts (via N-terminus) with NUFIP2 (By similarity). Interacts with NXF1; this interaction occurs in a mRNA-dependent and polyribosome-independent manner in the nucleus (By similarity). Interacts with NXF2 (via N-terminus); this interaction is direct and occurs in a NXF1 mRNA-containing mRNP complexes (PubMed:16790844, PubMed:17548835). Interacts with RANBP9; this interaction is direct and inhibits binding of FMR1 to RNA homomer (PubMed:15381419). Interacts with RPLP0 (PubMed:21784246). Interacts (via C-terminus) with SMN (via C-terminus); this interaction is direct and occurs in a RNA-independent manner (By similarity). Interacts with TDRD3 (via C-terminus); this interaction is direct (By similarity). Interacts with YBX1; this interaction occurs in association with polyribosome (PubMed:11162447). Interacts with nucleosome (By similarity). Associates with polyribosome; this association occurs in a mRNA-dependent manner (PubMed:8842725, PubMed:9285783, PubMed:12581522, PubMed:12575950, PubMed:14613971, PubMed:15317853, PubMed:15805463, PubMed:21784246). Associates with messenger ribonucleoprotein particles (mRNPs) (PubMed:8842725, PubMed:9285783, PubMed:11719188, PubMed:12581522, PubMed:12575950, PubMed:15329415, PubMed:18805096). Associates with microtubules in a kinesin- and dynein-dependent manner (PubMed:18539120). Interacts with HABP4 (By similarity).

EXTERNAL LINKS

Fmr1

Synaptic functional regulator FMR1

Fmr1

Molecular Synopsis