期刊
MOLECULAR CELL
卷 61, 期 5, 页码 760-773出版社
CELL PRESS
DOI: 10.1016/j.molcel.2016.02.013
关键词
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资金
- Cancer Research Institute
- D. M-E Ryder
- Leukemia & Lymphoma Society
- Smith Family Foundation
- NIGMS [GM100202]
- Fund for Medical Discovery fellowship
MicroRNAs predominantly decrease gene expression; however, specific mRNAs are translationally upregulated in quiescent (G0) mammalian cells and immature Xenopus laevis oocytes by an FXR1a-associated microRNA-protein complex (microRNP) that lacks the microRNP repressor, GW182. Their mechanism in these conditions of decreased mTOR signaling, and therefore reduced canonical (cap-and-poly(A)-tail-mediated) translation, remains undiscovered. Our data reveal that mTOR inhibition in human THP1 cells enables microRNA-mediated activation. Activation requires shortened/no poly(A)tail targets; polyadenylated mRNAs are partially activated upon PAIP2 overexpression, which interferes with poly(A)-bound PABP, precluding PABP-enhanced microRNA-mediated inhibition and canonical translation. Consistently, inhibition of PARN deadenylase prevents activation. P97/DAP5, a homolog of canonical translation factor, eIF4G, which lacks PABP-and cap binding complex-interacting domains, is required for activation, and thereby for the oocyte immature state. P97 interacts with 30 UTR-binding FXR1a-associated microRNPs and with PARN, which binds mRNA 50 caps, forming a specialized complex to translate recruited mRNAs in these altered canonical translation conditions.
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