Cell cycle-dependent regulation of Aurora kinase B mRNA by the Microprocessor complex
Eunsun Jung1, Youngmo Seong2, Jae Hong Seo3
1Department of Biomedical Sciences, Korea University College of Medicine, Seoul 136-705, Republic of Korea.
Biochemical and Biophysical Research Communications
|March 5, 2014
Summary
The Microprocessor complex controls cell division by degrading Aurora kinase B mRNA. This process is reduced during mitosis, allowing Aurora kinase B levels to rise, which is crucial for proper cell cycle progression.
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- Aurora kinase B is essential for chromosome segregation and the spindle checkpoint during mitosis.
- MicroRNA (miRNA) biogenesis involves the Microprocessor complex, which processes primary miRNA transcripts.
- Cell cycle progression is tightly regulated by the precise control of protein levels.
Purpose of the Study:
- To investigate the role of the Microprocessor complex in regulating Aurora kinase B mRNA stability.
- To elucidate the mechanism by which Microprocessor activity affects cell cycle progression.
- To identify factors involved in the regulation of Microprocessor activity during mitosis.
Main Methods:
- Quantification of Aurora kinase B mRNA and protein levels in human cells.
- Analysis of Microprocessor complex activity and its association with target transcripts.
- Investigation of the role of RNA helicases, specifically DDX5 and DDX17, in Microprocessor function.
Main Results:
- The Microprocessor complex directly cleaves and destabilizes Aurora kinase B mRNA in human cells.
- Microprocessor-mediated cleavage of Aurora kinase B mRNA prevents premature entry into mitosis.
- Cleavage activity of the Microprocessor complex is reduced during mitosis, leading to Aurora kinase B accumulation.
- The RNA helicase DDX5 is required for Microprocessor-mediated cleavage of Aurora kinase B mRNA.
- Association of DDX5 and DDX17 with the Microprocessor complex decreases during mitosis.
Conclusions:
- The Microprocessor complex acts as a negative regulator of Aurora kinase B mRNA stability.
- Reduced Microprocessor activity during mitosis allows for the accumulation of Aurora kinase B, facilitating mitotic progression.
- This study reveals a novel mechanism involving the Microprocessor complex and DDX5/DDX17 in regulating cell cycle progression through control of Aurora kinase B levels.
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