An evolutionarily conserved ribosome-rescue pathway maintains epidermal homeostasis
| Autor: | Ajay Kumar Mishra, Inês Sequeira, Tony Ly, Harunori Yoshikawa, Angus I. Lamond, Rachel Green, Kifayathullah Liakath-Ali, Fiona M. Watt, Angela Oliveira Pisco, Colin Chih Chien Wu, Kalle Sipilä, Eric W. Mills, Ibrahim M. Adham, Beate M. Lichtenberger |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Cellular differentiation Cell Cycle Proteins Nerve Tissue Proteins Receptors G-Protein-Coupled Mice 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation Animals Homeostasis RNA Messenger Mechanistic target of rapamycin PI3K/AKT/mTOR pathway Cell Proliferation Membrane Glycoproteins Multidisciplinary biology RNA quality control Cell growth Stem Cells TOR Serine-Threonine Kinases Microfilament Proteins Cell Differentiation Translation (biology) Endonucleases Biological Evolution Phenotype Ribosome skin stem cells Cell biology 030104 developmental biology Epidermal Cells Protein Biosynthesis TOR signalling Mutation Disease Progression biology.protein Female Epidermis Stem cell Ribosomes 030217 neurology & neurosurgery |
| Zdroj: | Liakath-Ali, K, Mills, E W, Sequeira, I, Lichtenberger, B M, Pisco, A O, Sipilä, K H, Mishra, A, Yoshikawa, H, Wu, C C-C, Ly, T, Lamond, A I, Adham, I M, Green, R & Watt, F M 2018, ' An evolutionarily conserved ribosome-rescue pathway maintains epidermal homeostasis ', Nature, vol. 556, pp. 376–380 . https://doi.org/10.1038/s41586-018-0032-3 |
| DOI: | 10.1038/s41586-018-0032-3 |
| Popis: | Ribosome-associated mRNA quality control mechanisms ensure the fidelity of protein translation1,2. Although these mechanisms have been extensively studied in yeast, little is known about their role in mammalian tissues, despite emerging evidence that stem cell fate is controlled by translational mechanisms3,4. One evolutionarily conserved component of the quality control machinery, Dom34 (in higher eukaryotes known as Pelota (Pelo)), rescues stalled ribosomes5. Here we show that Pelo is required for mammalian epidermal homeostasis. Conditional deletion of Pelo in mouse epidermal stem cells that express Lrig1 results in hyperproliferation and abnormal differentiation of these cells. By contrast, deletion of Pelo in Lgr5-expressing stem cells has no effect and deletion in Lgr6-expressing stem cells induces only a mild phenotype. Loss of Pelo results in accumulation of short ribosome footprints and global upregulation of translation, rather than affecting the expression of specific genes. Translational inhibition by rapamycin-mediated downregulation of mTOR (mechanistic target of rapamycin kinase) rescues the epidermal phenotype. Our study reveals that the ribosome-rescue machinery is important for mammalian tissue homeostasis and that it has specific effects on different stem cell populations. Loss of the ribosome-rescue factor Pelo in a subset of mouse epidermal stem cells results in hyperproliferation and altered differentiation of these cells. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|