Riassunto analitico
Many newly translated proteins undergo modifications that mediate their activity or localization.
Specifically, prenylation is a post-translational modification that controls protein localization by
attaching modular isoprene subunits to target proteins. This modification is crucial for stem cells
and regulates processes such as proliferation, differentiation, and migration. However, the
mechanism of how prenylation regulates stem cells during tissue regeneration in animals is not
well understood. To address this, we studied prenylation in planarians, Schmidtea mediterranea,
due to their abundant stem cell population and remarkable tissue regeneration capacity. We found
that planarians have all the genes required for the complete prenylation process. Disrupting
prenylation by silencing Geranylgeranyl pyrophosphate synthase (ggpps), a key enzyme for
isoprene biogenesis, using RNA interference, resulted in tissue disintegration and hampered tissue
regeneration. We also observed an accumulation of mitosis markers but no change to apoptosis,
and stem cells were resistant to apoptosis after irradiation, suggesting that ggpps may regulate the
stem cell cycle. Furthermore, the disruption of ggpps prevents stem cells from migrating to the
injury site. In situ hybridization and Single‐cell RNA sequencing indicate that ggpps is lowly
expressed broadly across all cell types, suggesting that ggpps might be an indispensable
housekeeping gene. To understand the dynamics of prenylated proteins during tissue regeneration,
we propose to integrate Immunoprecipitation with Mass Spectrometry. Bioinformatic predictions
by GPS-Lipid indicate that many GTPase proteins are likely prenylated. Protein mass spectrometry
will provide a comprehensive list of prenylated proteins, and their role in tissue regeneration will
remain the focus of future work.
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