A Drosophila fragile X protein interacts with components of RNAi and ribosomal proteins.

By A. Ishizuka, M. Siomi, H. Siomi. Genes & Development, 2002

635 citations recorded by the source corpus.

Fragile X syndrome is a common form of inherited mental retardation caused by the loss of FMR1 expression. The FMR1 gene encodes an RNA-binding protein that associates with translating ribosomes and acts as a negative translational regulator. In Drosophila, the fly homolog of the FMR1 protein (dFMR1) binds to and represses the translation of an mRNA encoding of the microtuble-associated protein Futsch. We have isolated a dFMR1-associated complex that includes two ribosomal proteins, L5 and L11, along with 5S RNA. The dFMR1 complex also contains Argonaute2 (AGO2) and a Drosophila homolog of p68 RNA helicase (Dmp68). AGO2 is an essential component for the RNA-induced silencing complex (RISC), a sequence-specific nuclease complex that mediates RNA interference (RNAi) in Drosophila. We show that Dmp68 is also required for efficient RNAi. We further show that dFMR1 is associated with Dicer, another essential component of the RNAi pathway, and microRNAs (miRNAs) in vivo, suggesting that dFMR1 is part of the RNAi-related apparatus. Our findings suggest a model in which the RNAi and dFMR1-mediated translational control pathways intersect in Drosophila. Our findings also raise the possibility that defects in an RNAi-related machinery may cause human disease.

Subfields: Genetics, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/76113622b0a11d72882ae3918ad1b4b8265dcbb7

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Citations in the corpus

Regulation of mRNA translation and stability by microRNAs. (2010, background): “One example is the fragile X mental retardation protein, FMRP, and its Drosophila ortholog, dFXR, which are RNAbinding proteins known to act as modulators of translation (71, 72).”
RNA Interference: Biology, Mechanism, and Applications (2003, background): “In other systems, Dicer has also been found to complex with various other proteins (35, 106).”
Diseases of Unstable Repeat Expansion: Mechanisms and Common Principles (2005, background): “Work in flies and mammals indicates that the RNAi pathway has a key role in the regulation of translation by FMR”
Extensive cross-regulation of post-transcriptional regulatory networks in Drosophila (2015, neutral): “FMR1forms acomplexwithcom-ponents of the RNAi machinery, including Argonaute 2 (AGO2), an essential component of the RNA-induced silencing complex (RISC) (Ishizuka et al. 2002).”
Fragile X Mental Retardation Protein: A Paradigm for Translational Control by RNA-Binding Proteins (2015, background): “, 2012)) along with 5S rRNA from whole cell extracts suggesting that FMRP could bind directly to the ribosome (Ishizuka et al., 2002).”
Perspective: machines for RNAi. (2005, background): “In fact, the Drosophila RISC com- 520 GENES & DEVELOPMENT ponent dFMR1 interacts directly with the ribosomal proteins L5 and L11 (Ishizuka et al. 2002).”
The microRNAs of Caenorhabditis elegans. (2003, background): “Perhaps the miRNAs are stabilized relative to their miRNA* fragments because they preferentially enter the miRNP/RISC complex.”
The action of ARGONAUTE1 in the miRNA pathway and its regulation by the miRNA pathway are crucial for plant development. (2004, background): “RISC-associated proteins also include the nuclease Tudor-SN, the putative RNA-binding VIG protein and the Fragile X-related protein (Hammond et al. 2001; Caudy et al. 2002, 2003; Hutvagner and Zamore 2002; Ishizuka et al. 2002; Martinez et al. 2002).”
The Drosha-DGCR8 complex in primary microRNA processing. (2004, background): “Although Dicer associates with several other proteins (Argonaute proteins in various organisms, RDE-4 in Caenorhabditis elegans, R2D2 in Drosophila, and dFMR1 in Drosophila) (Hammond et al. 2001; Ishizuka et al. 2002; Tabara et al. 2002; Liu et al. 2003), these interacting proteins do not seem to be”
MicroRNA gene expression deregulation in human breast cancer. (2005, background): “Deviations from normal pattern of expression may play a role in diseases, such as in neurologic disorders (3).”