Centriolar satellites regulate CEP350 mRNA stability and centrosome amplification

Area of Science:

• Cell Biology
• Molecular Biology
• Cancer Research

Background:

• Messenger RNAs (mRNAs) are known to accumulate at centrosomes during cell division and interphase.
• The precise mechanisms controlling mRNA localization and their functional roles at centrosomes are not well understood.

Purpose of the Study:

• To identify the molecular pathway regulating messenger RNA (mRNA) localization and stability at centrosomes.
• To investigate the role of this pathway in centriole duplication, specifically centriole overduplication.

Main Methods:

• Investigated mRNA localization to centrosomes using microscopy and identified key RNA-binding proteins (RBPs) and centriolar satellite proteins involved.
• Assessed the impact of manipulating specific proteins (UNK, CEP131) and pathways on CEP350 mRNA levels and stability.
• Examined the effects on centriole duplication, including canonical and overduplication, in various cell types, including triple-negative breast cancer cells.

Main Results:

• Identified a pathway involving the RNA-binding protein (RBP) UNK and centriolar satellite protein CEP131 that stabilizes CEP350 mRNA at centrosomes.
• CEP350 mRNA localization to centrosomes is microtubule-dependent during S phase.
• CEP350 is crucial for PLK4-induced centriole overduplication, with minimal impact on normal centriole duplication.
• Disruption of the identified pathway reduced centriole overduplication in cancer cells.

Conclusions:

• A novel centriolar satellite-RNA-binding protein (RBP) pathway regulates CEP350 mRNA localization and stability, supporting centriole overduplication.
• CEP131 and UNK are key components of this pathway and represent potential therapeutic targets to inhibit centriole overduplication in cancer.