|Title||Biochemical and genetic interaction between the fragile X mental retardation protein and the microRNA pathway.|
|Publication Type||Journal Article|
|Year of Publication||2004|
|Authors||Jin, P, Zarnescu, DC, Ceman, S, Nakamoto, M, Mowrey, J, Jongens, TA, Nelson, DL, Moses, K, Warren, ST|
|Date Published||2004 Feb|
|Keywords||Animals, Argonaute Proteins, Blotting, Western, Disease Models, Animal, Drosophila melanogaster, Drosophila Proteins, Eye, Fragile X Syndrome, HeLa Cells, Humans, Immunohistochemistry, Male, MicroRNAs, Microscopy, Electron, Scanning, Nerve Tissue Proteins, Neuromuscular Junction, Neuronal Plasticity, Precipitin Tests, Ribonuclease III, RNA-Induced Silencing Complex|
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.
|Alternate Journal||Nat. Neurosci.|