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07:23
Describing a Transcription Factor Dependent Regulation of the MicroRNA Transcriptome
Published on: June 15, 2016
Switching from repression to activation: microRNAs can up-regulate translation.
Shobha Vasudevan1, Yingchun Tong, Joan A Steitz
1Department of Molecular Biophysics and Biochemistry, Howard Hughes Medical Institute, Yale University School of Medicine, Boyer Center for Molecular Medicine, 295 Congress Avenue, New Haven, CT 06536, USA.
Science (New York, N.Y.)
|December 1, 2007
Summary
MicroRNAs (miRNAs) can activate gene translation during cell cycle arrest by binding to AU-rich elements (AREs) in messenger RNA (mRNA). This activation function of micro-ribonucleoproteins (miRNPs) appears to oscillate with cell proliferation.
Area of Science:
- Molecular Biology
- Gene Regulation
- Post-transcriptional Control
Background:
- AU-rich elements (AREs) and microRNA target sites in mRNA 3'UTRs regulate gene expression post-transcriptionally.
- During cell cycle arrest, AREs in tumor necrosis factor-alpha (TNFalpha) mRNA recruit Argonaute (AGO) and fragile X mental retardation-related protein 1 (FXR1), forming micro-ribonucleoproteins (miRNPs).
Purpose of the Study:
- To investigate the role of microRNA miR369-3 in directing protein association with AREs for translation activation.
- To determine if other microRNAs exhibit similar translation regulation patterns during cell cycle arrest and proliferation.
Main Methods:
- Investigated the interaction of miR369-3 with AREs and associated proteins (AGO, FXR1).
- Analyzed the translation regulation of target mRNAs by Let-7 and miRcxcr4 during cell cycle arrest and proliferation.
Main Results:
- Human microRNA miR369-3 directs AGO and FXR1 recruitment to AREs, activating mRNA translation.
- Let-7 and miRcxcr4 up-regulate target mRNA translation upon cell cycle arrest but repress it in proliferating cells.
- Translation activation by miRNPs is a common function observed during cell cycle arrest.
Conclusions:
- MicroRNA-mediated translation activation is a significant mechanism during cell cycle arrest.
- MicroRNA-ribonucleoprotein (miRNP) mediated translation regulation exhibits an oscillatory pattern between repression and activation throughout the cell cycle.
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