MyoIC’s effect on nucleolar structure and organization
Myosins are predominantly recognized for their role in muscle contraction and cellular cargo transport. Interestingly, one member of class IC myosin, MyolC16 (Nuclear Myosin I, NMI), exhibits localization within the nucleus and the nucleolus in addition to its cytoplasmic localization and functions. Our lab and others demonstrated that NMI and actin are important for rRNA transcription by RNAPI in the nucleolus. In addition, it was recently found to function in repairing heterochromatic DNA damage in mammalians. In parallel unrelated studies, it was shown how the integrity of DNA, RNAPI transcription, and rRNA aberrant transcription are highly correlated to cancer, extensive cell proliferation, and neurodegenerative diseases like Alzheimer’s and Parkinson’s diseases. We hypothesize that NMI utilizes its contractile activity to provide the nucleolus with its structure, function, and physiology. In my thesis, I aim to understand the molecular mechanism of NMI contractile activity in the dynamic nature of the nucleolus assembly essential for RNAPI transcription. Thus, my research aims to investigate the behavior and dynamics of the nucleolus at the molecular level. Using a genetic approach of Myo1C KD and Super Resolution Microscopy, I show that the presence of MyoIC necessitates the formation of nucleolar substructures. This and more provide a new frontier targeting Myo1C’s contribution to the pathophysiological manifestations of the unhealthy nucleolus as the initiator and propagator of neurodegenerative diseases.
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