Biochemical and genetic interaction between the fragile X mental retardation protein and the microRNA pathway.
Fragile X syndrome is caused by a loss of expression of the fragile X mental retardation protein (FMRP). FMRP is a selective RNA-binding protein which forms a messenger ribonucleoprotein (mRNP) complex that associates with polyribosomes. Recently, mRNA ligands associated with FMRP have been identified. However, the mechanism by which FMRP regulates the translation of its mRNA ligands remains unclear. MicroRNAs are small noncoding RNAs involved in translational control. Here we show that in vivo mammalian FMRP interacts with microRNAs and the components of the microRNA pathways including Dicer and the mammalian ortholog of Argonaute 1 (AGO1). Using two different Drosophila melanogaster models, we show that AGO1 is critical for FMRP function in neural development and synaptogenesis. Our results suggest that FMRP may regulate neuronal translation via microRNAs and links microRNAs with human disease.
Jin
Peng
P
Department of Human Genetics, Emory University, 615 Michael Street, Atlanta, Georgia 30322, USA.
Zarnescu
Daniela C
DC
Ceman
Stephanie
S
Nakamoto
Mika
M
Mowrey
Julie
J
Jongens
Thomas A
TA
Nelson
David L
DL
Moses
Kevin
K
Warren
Stephen T
ST
D000818:Animals; D060565:Argonaute Proteins; D015153:Blotting, Western; D004195:Disease Models, Animal; D029721:Drosophila Proteins / Q000378:metabolism; D004331:Drosophila melanogaster; D005123:Eye / Q000648:ultrastructure; D005600:Fragile X Syndrome / Q000235:genetics* / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D035683:MicroRNAs / Q000502:physiology*; D008855:Microscopy, Electron, Scanning; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism*; D009469:Neuromuscular Junction / Q000502:physiology / Q000648:ultrastructure; D009473:Neuronal Plasticity / Q000235:genetics; D011233:Precipitin Tests; D034743:RNA-Induced Silencing Complex / Q000378:metabolism; D043244:Ribonuclease III / Q000378:metabolism
C433807:AGO2 protein, Drosophila; D060565:Argonaute Proteins; D029721:Drosophila Proteins; D035683:MicroRNAs; D009419:Nerve Tissue Proteins; D034743:RNA-Induced Silencing Complex; D043244:Ribonuclease III