The fragile X mental retardation protein, FMRP, recognizes G-quartets.
Fragile X mental retardation is a disease caused by the loss of function of a single RNA-binding protein, FMRP. Identifying the RNA targets recognized by FMRP is likely to reveal much about its functions in controlling some aspects of memory and behavior. Recent evidence suggests that one of the predominant RNA motifs recognized by the FMRP protein is an intramolecular G-quartet and that the RGG box of FMRP mediates this interaction. Searching databases of mRNA sequence information, as well as compiled sequences of predicted FMRP targets based on biochemical identification, has revealed that many of these predicted FMRP targets contain intramolecular G-quartets. Interestingly, many of the G-quartet containing RNA targets encode proteins involved in neuronal development and synaptic function. Defects in the metabolism of this set of RNAs, presumably in the translation of their protein products, is likely to underlie the behavioral and cognitive changes seen in the disease.
The Rockefeller University, Laboratory of Molecular Neuro-Oncology New York, New York 10021, USA. darneie@rockefeller.edu
Jennifer C
JC
Darnell
Stephen T
ST
Warren
Robert B
RB
Darnell
D000818:Animals; D001483:Base Sequence; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1; D005600:Fragile X Syndrome / Q000235:genetics*; D006801:Humans; D008297:Male; D051379:Mice; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000502:physiology; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000032:analysis / Q000737:chemistry / Q000502:physiology*; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D051381:Rats
D051860:Fragile X Messenger Ribonucleoprotein 1; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C497683:FMR1 protein, human; C497684:Fmr1 protein, mouse; C497685:Fmr1 protein, rat