Methylation of the arginine-glycine-rich region in the fragile X mental retardation protein FMRP differentially affects RNA binding.
The C-terminal end of the fragile X mental retardation protein contains a stretch of amino acid residues that are enriched in arginine and glycine. Recent studies using recombinant FMRPs have demonstrated that this region participates in RNA binding in vitro, with calculated Kds ranging from 1-10 nM depending on the RNA. It is known that other arginine-glycine-rich proteins are subject to site-specific methylation by protein arginine methyltransferases (PRMTs) that are particularly abundant in most cells. We have demonstrated that the interaction of homoribopolymer mimetic RNAs with human FMRP (hFMRP) made in PRMT-containing cell-free lysates is more sensitive to increasing salt concentrations than recombinant hFMRP expressed in bacteria. We have also shown that blocking methylation with adenosine-2', 3'-dialdehyde (AdOx) alters homoribopolymer binding and hFMRP target mRNA binding; both increases and decreases are observed as a function of methylation. These data suggest that changes in PRMT activity that occur during development, or arise via signal transduction may be a means of regulating the binding of hFMRP to mRNA in vivo.
Denman
Robert B
RB
New York State Institute for Basic Research, Department of Molecular Biology, Laboratory of Biochemical Molecular Neurobiology, 1050 Forest Hill Road Staten Island, NY 10314, USA.
D001120:Arginine; D001665:Binding Sites; D003001:Cloning, Molecular; D019175:DNA Methylation; D004926:Escherichia coli / Q000235:genetics; D051860:Fragile X Messenger Ribonucleoprotein 1; D005600:Fragile X Syndrome / Q000235:genetics*; D005998:Glycine; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D012313:RNA / Q000378:metabolism*; D016601:RNA-Binding Proteins; D011994:Recombinant Proteins / Q000378:metabolism; D014158:Transcription, Genetic
D001120:Arginine; D051860:Fragile X Messenger Ribonucleoprotein 1; D005998:Glycine; D009419:Nerve Tissue Proteins; D012313:RNA; D016601:RNA-Binding Proteins; D011994:Recombinant Proteins; C497683:FMR1 protein, human