Fragile X mental retardation protein targets G quartet mRNAs important for neuronal function.
Loss of fragile X mental retardation protein (FMRP) function causes the fragile X mental retardation syndrome. FMRP harbors three RNA binding domains, associates with polysomes, and is thought to regulate mRNA translation and/or localization, but the RNAs to which it binds are unknown. We have used RNA selection to demonstrate that the FMRP RGG box binds intramolecular G quartets. This data allowed us to identify mRNAs encoding proteins involved in synaptic or developmental neurobiology that harbor FMRP binding elements. The majority of these mRNAs have an altered polysome association in fragile X patient cells. These data demonstrate that G quartets serve as physiologically relevant targets for FMRP and identify mRNAs whose dysregulation may underlie human mental retardation.
Darnell
J C
JC
Laboratory of Molecular Neuro-Oncology, The Rockefeller University, New York, NY 10021, USA.
Jensen
K B
KB
Jin
P
P
Brown
V
V
Warren
S T
ST
Darnell
R B
RB
D001483:Base Sequence; D001665:Binding Sites; D003062:Codon; D016384:Consensus Sequence; D018076:DNA, Complementary / Q000235:genetics; D003712:Dendrites / Q000502:physiology; D051860:Fragile X Messenger Ribonucleoprotein 1; D005600:Fragile X Syndrome / Q000235:genetics*; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D008024:Ligands; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D009690:Nucleic Acid Conformation; D017924:Nucleopolyhedroviruses / Q000235:genetics; D011485:Protein Binding; D014176:Protein Biosynthesis; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D012045:Regulatory Sequences, Nucleic Acid; D012270:Ribosomes / Q000378:metabolism; D016415:Sequence Alignment; D013569:Synapses / Q000502:physiology
D003062:Codon; D018076:DNA, Complementary; D051860:Fragile X Messenger Ribonucleoprotein 1; D008024:Ligands; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C497683:FMR1 protein, human