Functionally diverse MicroRNA effector complexes are regulated by extracellular signaling

Pei Hsuan Wu; Mamiko Isaji; Richard W. Carthew

doi:10.1016/j.molcel.2013.08.023

Functionally diverse MicroRNA effector complexes are regulated by extracellular signaling

Pei Hsuan Wu, Mamiko Isaji, Richard W. Carthew^*

^*Corresponding author for this work

Molecular Biosciences

Research output: Contribution to journal › Article › peer-review

46 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	113-123
Number of pages	11
Journal	Molecular cell
Volume	52
Issue number	1
DOIs	https://doi.org/10.1016/j.molcel.2013.08.023
State	Published - Oct 10 2013

Funding

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.).

ASJC Scopus subject areas

Molecular Biology
Cell Biology

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.molcel.2013.08.023

Cite this

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title = "Functionally diverse MicroRNA effector complexes are regulated by extracellular signaling",

abstract = "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.",

author = "Wu, \{Pei Hsuan\} and Mamiko Isaji and Carthew, \{Richard W.\}",

note = "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{\textquoteright}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.). ",

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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.

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Functionally diverse MicroRNA effector complexes are regulated by extracellular signaling

Abstract

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ASJC Scopus subject areas

UN SDGs

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