Functionally diverse MicroRNA effector complexes are regulated by extracellular signaling

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

*Corresponding author for this work

Research output: Contribution to journalArticle

37 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 languageEnglish (US)
Pages (from-to)113-123
Number of pages11
JournalMolecular cell
Volume52
Issue number1
DOIs
StatePublished - Oct 10 2013

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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