Functionally diverse microRNA effector complexes are regulated by extracellular signaling.
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.
Department of Molecular Biosciences, Northwestern University, Evanston, IL 60208, USA.
Pei-Hsuan
PH
Wu
Mamiko
M
Isaji
Richard W
RW
Carthew
D000818:Animals; D060565:Argonaute Proteins / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D029721:Drosophila Proteins / Q000378:metabolism; D004331:Drosophila melanogaster; D005786:Gene Expression Regulation; D020868:Gene Silencing; D007328:Insulin / Q000378:metabolism; D050356:Lipid Metabolism; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008934:Mitogens / Q000494:pharmacology; D011132:Polyribosomes / Q000378:metabolism; D034622:RNA Interference; D016601:RNA-Binding Proteins / Q000378:metabolism; D034743:RNA-Induced Silencing Complex / Q000235:genetics / Q000378:metabolism*; D044967:Serum / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors; D014162:Transfection
C489654:AGO1 protein, Drosophila; D060565:Argonaute Proteins; D029721:Drosophila Proteins; C513405:Gw protein, Drosophila; D007328:Insulin; C503213:Loqs protein, Drosophila; D035683:MicroRNAs; D008934:Mitogens; D016601:RNA-Binding Proteins; D034743:RNA-Induced Silencing Complex; D013755:Tetradecanoylphorbol Acetate