Multi-functional regulation of 4E-BP gene expression by the Ccr4-Not complex

PloS One
Hirokazu OkadaErnst Hafen

Abstract

The mechanistic target of rapamycin (mTOR) signaling pathway is highly conserved from yeast to humans. It senses various environmental cues to regulate cellular growth and homeostasis. Deregulation of the pathway has been implicated in many pathological conditions including cancer. Phosphorylation cascades through the pathway have been extensively studied but not much is known about the regulation of gene expression of the pathway components. Here, we report that the mRNA level of eukaryotic translation initiation factor (eIF) subunit 4E-binding protein (4E-BP) gene, one of the key mTOR signaling components, is regulated by the highly conserved Ccr4-Not complex. RNAi knockdown of Not1, a putative scaffold protein of this protein complex, increases the mRNA level of 4E-BP in Drosophila Kc cells. Examination of the gene expression mechanism using reporter swap constructs reveals that Not1 depletion increases reporter mRNAs with the 3'UTR of 4E-BP gene, but decreases the ones with the 4E-BP promoter region, suggesting that Ccr4-Not complex regulates both degradation and transcription of 4E-BP mRNA. These results indicate that the Ccr4-Not complex controls expression of a single gene at multiple levels and adjusts the magnitude of ...Continue Reading

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Citations

Aug 16, 2018·Wiley Interdisciplinary Reviews. RNA·Benjamin P Towler, Sarah F Newbury
Aug 14, 2020·Wiley Interdisciplinary Reviews. RNA·Yong-Bin Yan
Jun 16, 2017·Scientific Reports·Alfonso Rodríguez-GilM Lienhard Schmitz

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Methods Mentioned

BETA
GTPase
ubiquitination
transfection
PCR
in vitro transcription
PCRs

Software Mentioned

Image J
FlowJo

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