Centriolar satellites regulate CEP350 mRNA localization and centrosome amplification

Area of Science:

• Cell Biology
• Molecular Biology
• Cancer Research

Background:

• Messenger RNAs (mRNAs) are known to accumulate at centrosomes, but the mechanisms and functional importance of this localization are not fully understood.
• Centrosomal localization of specific mRNAs, such as those encoding centrosomal proteins, occurs during interphase, yet the underlying processes remain unclear.

Purpose of the Study:

• To investigate the regulation and function of the centrosome-localized mRNA, CEP350.
• To elucidate the mechanisms governing CEP350 mRNA localization to centrosomes and its functional significance.

Main Methods:

• Investigated mRNA localization using techniques to track CEP350 mRNA.
• Utilized RNA binding protein (RBP) and protein interaction studies.
• Examined microtubule (MT) dependence of mRNA localization.
• Assessed the role of identified proteins in centriole duplication and centrosome amplification.

Main Results:

• CEP350 mRNA localizes to centrosomes during S phase, dependent on CEP131 and Unkempt (UNK) in a microtubule-dependent manner.
• CEP131 and UNK stabilize CEP350 mRNA, maintaining its steady-state levels and promoting normal CEP350 protein levels at centrosomes.
• CEP350 is essential for PLK4-induced centriole overduplication and plays a role in centrosome amplification in triple-negative breast cancer cells.

Conclusions:

• A novel centriolar satellite-RNA binding protein (RBP) pathway regulates CEP350 mRNA localization to centrosomes.
• CEP131, UNK, and CEP350 are critical for centrosome amplification in triple-negative breast cancer, identifying them as potential therapeutic targets.