Recombinant Human Fragile X mental retardation syndrome-related protein 1 (FXR1)

Function

mRNA-binding protein that acts as a regulator of mRNAs translation and/or stability, and which is required for various processes, such as neurogenesis, muscle development and spermatogenesis (PubMed:17382880, PubMed:20417602, PubMed:30067974, PubMed:34731628, PubMed:35989368, PubMed:36306353). Specifically binds to AU-rich elements (AREs) in the 3'-UTR of target mRNAs (PubMed:17382880, PubMed:34731628). Promotes formation of some phase-separated membraneless compartment by undergoing liquid-liquid phase separation upon binding to AREs-containing mRNAs, leading to assemble mRNAs into cytoplasmic ribonucleoprotein granules that concentrate mRNAs with associated regulatory factors (By similarity). Required to activate translation of stored mRNAs during late spermatogenesis: acts by undergoing liquid-liquid phase separation to assemble target mRNAs into cytoplasmic ribonucleoprotein granules that recruit translation initiation factor EIF4G3 to activate translation of stored mRNAs in late spermatids (By similarity). Promotes translation of MYC transcripts by recruiting the eIF4F complex to the translation start site (PubMed:34731628). Acts as a negative regulator of inflammation in response to IL19 by promoting destabilization of pro-inflammatory transcripts (PubMed:30067974). Also acts as an inhibitor of inflammation by binding to TNF mRNA, decreasing TNF protein production (By similarity). Acts as a negative regulator of AMPA receptor GRIA2/GluA2 synthesis during long-lasting synaptic potentiation of hippocampal neurons by binding to GRIA2/GluA2 mRNA, thereby inhibiting its translation (By similarity). Regulates proliferation of adult neural stem cells by binding to CDKN1A mRNA and promoting its expression (By similarity). Acts as a regulator of sleep and synaptic homeostasis by regulating translation of transcripts in neurons (By similarity). Required for embryonic and postnatal development of muscle tissue by undergoing liquid-liquid phase separation to assemble target mRNAs into cytoplasmic ribonucleoprotein granules (PubMed:30770808). Involved in the nuclear pore complex localization to the nuclear envelope by preventing cytoplasmic aggregation of nucleoporins: acts by preventing ectopic phase separation of nucleoporins in the cytoplasm via a microtubule-dependent mechanism (PubMed:32706158). Plays a role in the stabilization of PKP2 mRNA and therefore protein abundance, via its interaction with PKP3 (PubMed:25225333). May also do the same for PKP2, PKP3 and DSP via its interaction with PKP1 (PubMed:25225333). Forms a cytoplasmic messenger ribonucleoprotein (mRNP) network by packaging long mRNAs, serving as a scaffold that recruits proteins and signaling molecules. This network facilitates signaling reactions by maintaining proximity between kinases and substrates, crucial for processes like actomyosin reorganization (PubMed:39106863)

Subcellular Location

Cytoplasm, Cytoplasmic ribonucleoprotein granule; Cytoplasm, Stress granule; Cytoplasm; Cell projection, dendrite; Cell projection, dendritic spine; Cell projection, axon; Nucleus envelope; Postsynapse

Disease Association

Congenital myopathy 9A (CMYO9A) : An autosomal recessive muscular disorder characterized by severe hypotonia apparent at birth, poor feeding, ulnar deviation of the hands, laterally deviated feet, fractures of the long bones, respiratory insufficiency due to muscle weakness, and death in infancy. [The disease is caused by variants affecting the gene represented in this entry] | Congenital myopathy 9B, proximal, with minicore lesions (CMYO9B) : An autosomal recessive, slowly progressive muscular disorder characterized by primarily proximal muscle weakness, neonatal hypotonia leading to delayed motor development, mildly delayed walking in childhood, and difficulty running or climbing. Cardiac function is unaffected, but most patients have obstructive sleep apnea. Muscle biopsy shows type 1 fiber predominance with disorganized Z-lines and minicores that disrupt the myofibrillar striation pattern. [The disease is caused by variants affecting the gene represented in this entry]

Tissue Specificity

Expressed in all tissues examined including heart, brain, kidney and testis (PubMed:7781595, PubMed:9259278). In brain, present at high level in neurons and especially in the Purkinje cells at the interface between the granular layer and the molecular layer (at protein level) (PubMed:9259278)

Subunit

(Microbial infection) Interacts with Sindbis virus non-structural protein 3 (via C-terminus); this interaction inhibits the formation of host stress granules on viral mRNAs and the nsp3-FXR1 complexes bind viral RNAs and probably orchestrate the assembly of viral replication complexes

• Siomi M.C. et al. FXR1, an autosomal homolog of the fragile X mental retardation gene. — EMBO J. (1995)
• Xu Z.Y. et al. Identification of alternatively spliced genes related to spermatogenesis using cDNA microarrays. (JUL-)
• Ota T. et al. Complete sequencing and characterization of 21,243 full-length human cDNAs. — Nat. Genet. (2004)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)
• Bienvenut W.V. et al. PubMed: CI-DIOL42GITMQ1H (MAR-)
• Zhang Y. et al. The fragile X mental retardation syndrome protein interacts with novel homologs FXR1 and FXR2. — EMBO J. (1995)
• Siomi M.C. et al. Specific sequences in the fragile X syndrome protein FMR1 and the FXR proteins mediate their binding to 60S ribosomal subunits and the interactions among them. — Mol. Cell. Biol. (1996)
• Tamanini F. et al. Differential expression of FMR1, FXR1 and FXR2 proteins in human brain and testis. — Hum. Mol. Genet. (1997)