An Unexpected Role for RNA Methylation in Mitosis Leads to New Understanding of Neurodevelopmental Disorders

Traditionally, RNA methylation has been studied in the context of gene expression regulation, RNA stability and translation efficiency, with its primary role thought to be in modulating cellular homeostasis and protein synthesis. However, a 2025 study by Dharmadkikari and colleagues uncovers an unexpected and critical function for RNA methylation in mitotic spindle integrity.

False color transmission electron microscope (TEM) micrograph of a mitotic cell in metaphase stage showing chromosomes (purple) in the equatorial plane and one of the mitotic spindle poles (blue). Mutations in SPOUT1/CENP-32 affect RNA methylation which is necessary for proper cell division.
False color transmission electron microscope (TEM) micrograph of a mitotic cell in metaphase stage showing chromosomes (purple) in the equatorial plane and one of the mitotic spindle poles (blue).

The study identifies a critical role for SPOUT1/CENP-32-dependent methylation in mitotic spindle formation and accurate chromosome segregation. Originally identified in a large-scale analysis of proteins associated with mitotic chromosomes, SPOUT1/CENP-32 encodes a putative RNA methyltransferase. The protein localizes to mitotic spindles, and when it is absent centrosome detachment from the spindle poles, delayed anaphase, and chromosome segregation errors are observed. Further, CRISPR experiments in human cells show that the protein is essential for cell viability.

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Stop Targeting Lasers on My Chromosomes!

The phases of the cell cycle, particularly that of mitosis, were taught in college as part of my studies in biology. The cell cycle is a fundamental process for all organisms and constantly happens within our bodies. While cells generally spend most of the time in interphase, many scientists focus on what happens as the cells prepare to divide from one cell into two. Mitosis, the part of the cell cycle that refers to cell division, is subject to extensive regulation to ensure all materials and genetic information are sound and ready to segregate correctly. If there is damage to the chromosomes, the cells will halt cell division. Continue reading “Stop Targeting Lasers on My Chromosomes!”