NF45 and NF90 Regulate Mitotic Gene Expression by Competing with Staufen-Mediated mRNA Decay

Area of Science:

• Molecular Biology
• Cell Biology
• Genetics

Background:

• Cell cycle progression involves precise regulation of gene expression.
• While transcriptional control is well-studied, post-transcriptional regulation of cell cycle genes remains less understood.
• RNA-binding proteins (RBPs) are key regulators of mRNA fate.

Purpose of the Study:

• To identify RBPs involved in cell cycle gene regulation.
• To elucidate the role of specific RBPs, NF45 and NF90, in mitosis.
• To understand the mechanism by which NF45 and NF90 regulate mitotic mRNAs.

Main Methods:

• Analysis of gene expression signatures of 687 RBPs.
• Correlation analysis to identify RBPs linked to cell cycle mRNAs.
• Transcriptome analysis to assess the necessity of NF45 and NF90 for mitotic gene expression.
• Proteomics to identify protein complexes associated with NF45-NF90.
• Functional assays to study the impact of SMD component depletion.

Main Results:

• Identified 39 RBPs correlating with cell cycle mRNAs.
• NF45 and NF90 were found to be essential for mitosis.
• NF45-NF90 complex regulates a subset of mitotic mRNAs.
• Proteomic analysis linked NF45-NF90 to Staufen-mediated mRNA decay (SMD) components.
• Depletion of SMD components enhanced mitotic mRNA binding to NF45-NF90 and rescued mitotic defects.

Conclusions:

• The NF45-NF90 complex plays a critical role in mitosis.
• NF45-NF90 regulates mitotic gene expression by competing with the SMD machinery for target mRNAs.
• This competition mechanism is vital for proper cell cycle progression and mitotic fidelity.