Mitotic control by mRNA splicing regulators ensures primary cilia formation

Area of Science:

• Cell Biology
• Molecular Biology
• Developmental Biology

Background:

• Primary cilium biogenesis is tightly linked to cell cycle progression, with cells exiting the cell cycle to form cilia and re-entering to resorb them.
• Previous research identified mechanisms connecting cell cycle progression and ciliogenesis through genome-wide RNAi screening.

Purpose of the Study:

• To investigate the impact of mRNA splicing on primary cilia assembly following mitosis.
• To elucidate the role of specific splicing regulators in the cell cycle exit and ciliogenesis process.

Main Methods:

• Utilized high-content genome-wide RNAi screening in hTERT-RPE1 cells.
• Investigated the effects of knocking down splicing regulators (SON, XAB2) on cell cycle progression and ciliogenesis.
• Employed a spliceosome inhibitor (SSA) to assess the impact of general mRNA splicing inhibition on cilia assembly.
• Examined ciliary defects in zebrafish embryos treated with SSA.

Main Results:

• Knockdown of splicing regulators SON and XAB2 led to abnormal G2/M cell cycle arrest, indicating impaired mitosis exit.
• Inhibition of mRNA splicing using SSA resulted in ciliogenesis defects in cell culture.
• SSA treatment in zebrafish embryos caused abnormal vascular development, a phenotype associated with ciliary dysfunction.

Conclusions:

• mRNA splicing regulators, including SON and XAB2, play a critical role in regulating mitosis exit, which is essential for ciliogenesis.
• Proper mRNA splicing is vital for primary cilia assembly and overall cellular function.
• These findings highlight the intricate connection between mRNA splicing, cell cycle regulation, and ciliogenesis, with implications for developmental processes.