The effect of SMN depletion on the cell cycle
Year: 2025
Type: dissertation
Abstract: Spinal muscular atrophy (SMA) is a severe neurodegenerative disorder caused by a mutation of the SMN1 gene, resulting in reduced levels of the survival motor neuron (SMN) protein. While SMN's role in small nuclear ribonucleoprotein (snRNP) biogenesis and pre-mRNA splicing is well documented, its function in cell cycle regulation remains largely unexplored. This study examines how SMN depletion influences cell cycle progression in HeLa cells using a doxycycline-inducible short hairpin RNA (shRNA) system to knock down SMN expression. To visualize cell cycle dynamics in live cells, I employed the Fucci5 dual-fluorescent reporter system, which enables real-time tracking of specific cell cycle phases through the regulated expression of Cdt1 and Geminin. Flow cytometry and fluorescence microscopy revealed that SMN depletion leads to an increase of cells in the sub-G1 phase. These results suggest that SMN plays a broader regulatory role, extending beyond RNA metabolism, and potentially influencing the molecular machinery that governs cell proliferation. Our findings expand the functional landscape of SMN and provide new insights into its cellular roles, which may have implications for understanding the pathophysiology of SMA and guiding the development of novel therapeutic strategies.
DOI: 10.17918/00011132
Authors: Maria Ruiz, Eishi Noguchi
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: gold
OpenAlex ID: W4413281560