TY - JOUR
T1 - Functionally diverse MicroRNA effector complexes are regulated by extracellular signaling
AU - Wu, Pei Hsuan
AU - Isaji, Mamiko
AU - Carthew, Richard W.
N1 - Funding Information:
We thank N. Colley, G. Hannon, C. Horvath, A. Nakamura, C. Petersen, A. Simmons, H. Siomi, and M. Siomi for gifts of reagents. We also thank the O. Uhlenbeck and R. Lamb’s labs for sharing centrifuges and A. Wanless and R. Patterson for their valuable assistance. We are indebted to the Developmental Hybridoma Studies Bank and Flybase for their resources. We thank our lab colleagues for advice and help. Funding support is gratefully acknowledged from the American Heart Association (to P.-H.W.) and the National Institutes of Health (GM068743 and GM077581) (to R.W.C.).
PY - 2013/10/10
Y1 - 2013/10/10
N2 - 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, iscomprised 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.
AB - 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, iscomprised 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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U2 - 10.1016/j.molcel.2013.08.023
DO - 10.1016/j.molcel.2013.08.023
M3 - Article
C2 - 24055343
AN - SCOPUS:84885351670
SN - 1097-2765
VL - 52
SP - 113
EP - 123
JO - Molecular Cell
JF - Molecular Cell
IS - 1
ER -