Because microRNAs (miRNAs) influence the expression of many genes in cells, discovering how the miRNA pathway is regulated is an important area of investigation. We found that the Drosophila miRNA-induced silencing complex (miRISC) exists in multiple forms. A constitutive form, called G-miRISC, is comprised of Ago1, miRNA, and GW182. Two distinct miRISC complexes that lack GW182 are regulated by mitogenic signaling. Exposure of cells to serum, lipids, or the tumor promoter PMA suppressed formation of these complexes. P-miRISC is comprised of Ago1, miRNA, and Loqs-PB, and it associates with mRNAs assembled into polysomes. The other regulated Ago1 complex associates with membranous organelles and is likely an intermediate in miRISC recycling. The formation of these complexes is correlated with a 5- to 10-fold stronger repression of target gene expression inside cells. Taken together, these results indicate that mitogenic signaling regulates the miRNA effector machinery to attenuate its repressive activities.
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http://dx.doi.org/10.1016/j.molcel.2013.08.023 | DOI Listing |
Front Cell Infect Microbiol
August 2024
Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
Neurol Neuroimmunol Neuroinflamm
May 2023
From the Department of Neurology (C.P.M., P.-B.V., K.F., J.-P.C., J.-C.G.A.), University Hospital of Saint-Etienne; Synaptopathies and Autoantibodies (SynatAc) Team (C.P.M., Y.T., L.-D.D., S.M.-C., V.R., K.F., C.L.M., J.H., J.-P.C., J.-C.G.A.), Institut NeuroMyoGène, MELIS, INSERM U1314/CNRS UMR 5284, Université Claude Bernard Lyon 1; Faculty of Medicine (C.P.M., Y.T., J.-P.C., J.-C.G.A.), University Jean Monnet, Saint-Étienne, Saint-Priest-en-Jarez; Department of Biochemistry (Y.T., C.L.M.), University Hospital of Saint-Etienne; French Reference Center on Paraneoplastic Neurological Syndrome (L.-D.D., S.M.-C., V.R., J.H., J.-P.C., J.-C.G.A.), Hospices Civils de Lyon, Hôpital Neurologique, Bron; Department of Internal Medicine (M.K.), University Hospital of Saint-Etienne; CIRI-Centre International de Recherche en Infectiologie (M.K., S.P.), Team GIMAP (Saint-Etienne), Université Claude Bernard Lyon 1, Inserm, U1111, CNRS, UMR5308, ENS Lyon, UJM; CIC Inserm 1408 Vaccinology (M.K., S.P.), Saint-Etienne; Department of Immunology (S.P.), University Hospital of Saint-Etienne; and European Reference Center for Rare Neuromuscular Diseases (J.-P.C., J.-C.G.A.), Saint-Etienne Cedex 02, France.
Background And Objectives: Autoantibodies (Abs) improve diagnosis and treatment decisions of idiopathic neurologic disorders. Recently, we identified Abs against Argonaute (AGO) proteins as potential autoimmunity biomarkers in neurologic disorders. In this study, we aim to reveal (1) the frequency of AGO1 Abs in sensory neuronopathy (SNN), (2) titers and IgG subclasses, and (3) their clinical pattern including response to treatment.
View Article and Find Full Text PDFInt J Mol Sci
September 2022
Department of Pharmaceutical Microbiology and Microbiological Diagnostic, Medical University of Lodz, Muszynskiego St. 1, 90-151 Lodz, Poland.
Argonaute (AGO) proteins, through their key role in the regulation of gene expression, participate in many biological processes, including cell differentiation, proliferation, death and DNA repair. Accurate regulation of gene expression appears to be important for the proper development of complex neural circuits. Loss of AGO proteins is known to lead to early embryonic mortality in mice with various malformations, including anomalies of the central nervous system.
View Article and Find Full Text PDFCell Host Microbe
May 2021
Laboratory of Virology and Infectious Disease, the Rockefeller University, New York, NY 10065, USA. Electronic address:
Argonaute (AGO) proteins bind small RNAs to silence complementary RNA transcripts, and they are central to RNA interference (RNAi). RNAi is critical for regulation of gene expression and antiviral defense in Aedes aegypti mosquitoes, which transmit Zika, chikungunya, dengue, and yellow fever viruses. In mosquitoes, AGO1 mediates miRNA interactions, while AGO2 mediates siRNA interactions.
View Article and Find Full Text PDFACS Chem Biol
February 2020
Department of Chemistry , The Scripps Research Institute, 110 Scripps Way , Jupiter , Florida 33458 , United States.
Myotonic dystrophy type 2 (DM2) is a genetically defined muscular dystrophy that is caused by an expanded repeat of r(CCUG) [r(CCUG)] in intron 1 of a CHC-type zinc finger nucleic acid binding protein () pre-mRNA. Various mechanisms contribute to DM2 pathology including pre-mRNA splicing defects caused by sequestration of the RNA splicing regulator muscleblind-like-1 (MBNL1) by r(CCUG). Herein, we study the biological impacts of the molecular recognition of r(CCUG)'s structure by a designer dimeric small molecule that directly cleaves the RNA in patient-derived cells.
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