publication . Article . Other literature type . 2016

Stem cell function and stress response are controlled by protein synthesis

Sandra Blanco; Rosana Garrido; Michaela Frye;
Open Access English
  • Published: 01 Jun 2016
  • Publisher: Nature Publishing Group
  • Country: United Kingdom
Abstract
Whether protein synthesis and cellular stress response pathways interact to control stem cell function is currently unknown. Here we show that mouse skin stem cells synthesize less protein than their immediate progenitors in vivo, even when forced to proliferate. Our analyses reveal that activation of stress response pathways drives both a global reduction of protein synthesis and altered translational programmes that together promote stem cell functions and tumorigenesis. Mechanistically, we show that inhibition of post-transcriptional cytosine-5 methylation locks tumour-initiating cells in this distinct translational inhibition programme. Paradoxically, this i...
Subjects
free text keywords: Article, Multidisciplinary
Related Organizations
Funded by
WT
Project
  • Funder: Wellcome Trust (WT)
70 references, page 1 of 5

Blanco, S. Aberrant methylation of tRNAs links cellular stress to neuro-developmental disorders. The EMBO journal. 2014; 33: 2020-2039 [OpenAIRE] [PubMed] [DOI]

Tuorto, F. RNA cytosine methylation by Dnmt2 and NSun2 promotes tRNA stability and protein synthesis. Nat Struct Mol Biol. 2012; 19: 900-905 [OpenAIRE] [PubMed] [DOI]

Schaefer, M. RNA methylation by Dnmt2 protects transfer RNAs against stress-induced cleavage. Genes Dev. 2010; 24: 1590-1595 [OpenAIRE] [PubMed] [DOI]

Ivanov, P, Emara, MM, Villen, J, Gygi, SP, Anderson, P. Angiogenin-induced tRNA fragments inhibit translation initiation. Mol Cell. 2011; 43: 613-623 [OpenAIRE] [PubMed] [DOI]

Spriggs, KA, Bushell, M, Willis, A. Translational regulation of gene expression during conditions of cell stress. Mol Cell. 2010; 40: 228-237 [OpenAIRE] [PubMed] [DOI]

Sobala, A, Hutvagner, G. Small RNAs derived from the 5' end of tRNA can inhibit protein translation in human cells. RNA Biol. 2013; 10: 553-563 [OpenAIRE] [PubMed] [DOI]

Gebetsberger, J, Zywicki, M, Kunzi, A, Polacek, N. tRNA-derived fragments target the ribosome and function as regulatory non-coding RNA in Haloferax volcanii. Archaea. 2012; 2012: 260909 [OpenAIRE] [PubMed] [DOI]

Khan, MA. Mutation in NSUN2, which Encodes an RNA Methyltransferase, Causes Autosomal-Recessive Intellectual Disability. Am J Hum Genet. 2012; 90: 856-863 [OpenAIRE] [PubMed] [DOI]

Martinez, FJ. Whole exome sequencing identifies a splicing mutation in NSUN2 as a cause of a Dubowitz-like syndrome. J Med Genet. 2012; 49: 380-385 [OpenAIRE] [PubMed] [DOI]

Abbasi-Moheb, L. Mutations in NSUN2 cause autosomal-recessive intellectual disability. Am J Hum Genet. 2012; 90: 847-855 [OpenAIRE] [PubMed] [DOI]

Blanco, S. The RNA-methyltransferase Misu (NSun2) poises epidermal stem cells to differentiate. PLoS Genet. 2011; 7: e1002403 [OpenAIRE] [PubMed] [DOI]

Hussain, S. The Mouse Cytosine-5 RNA Methyltransferase NSun2 Is a Component of the Chromatoid Body and Required for Testis Differentiation. Mol Cell Biol. 2013; 33: 1561-1570 [OpenAIRE] [PubMed] [DOI]

Fuchs, E. Cell biology: More than skin deep. J Cell Biol. 2015; 209: 629-631 [OpenAIRE] [PubMed] [DOI]

Plikus, MV, Chuong, CM. Macroenvironmental regulation of hair cycling and collective regenerative behavior. Cold Spring Harbor perspectives in medicine. 2014; 4: a015198 [OpenAIRE] [PubMed] [DOI]

Muller-Rover, S. A comprehensive guide for the accurate classification of murine hair follicles in distinct hair cycle stages. J Invest Dermatol. 2001; 117: 3-15 [OpenAIRE] [PubMed] [DOI]

70 references, page 1 of 5
Abstract
Whether protein synthesis and cellular stress response pathways interact to control stem cell function is currently unknown. Here we show that mouse skin stem cells synthesize less protein than their immediate progenitors in vivo, even when forced to proliferate. Our analyses reveal that activation of stress response pathways drives both a global reduction of protein synthesis and altered translational programmes that together promote stem cell functions and tumorigenesis. Mechanistically, we show that inhibition of post-transcriptional cytosine-5 methylation locks tumour-initiating cells in this distinct translational inhibition programme. Paradoxically, this i...
Subjects
free text keywords: Article, Multidisciplinary
Related Organizations
Funded by
WT
Project
  • Funder: Wellcome Trust (WT)
70 references, page 1 of 5

Blanco, S. Aberrant methylation of tRNAs links cellular stress to neuro-developmental disorders. The EMBO journal. 2014; 33: 2020-2039 [OpenAIRE] [PubMed] [DOI]

Tuorto, F. RNA cytosine methylation by Dnmt2 and NSun2 promotes tRNA stability and protein synthesis. Nat Struct Mol Biol. 2012; 19: 900-905 [OpenAIRE] [PubMed] [DOI]

Schaefer, M. RNA methylation by Dnmt2 protects transfer RNAs against stress-induced cleavage. Genes Dev. 2010; 24: 1590-1595 [OpenAIRE] [PubMed] [DOI]

Ivanov, P, Emara, MM, Villen, J, Gygi, SP, Anderson, P. Angiogenin-induced tRNA fragments inhibit translation initiation. Mol Cell. 2011; 43: 613-623 [OpenAIRE] [PubMed] [DOI]

Spriggs, KA, Bushell, M, Willis, A. Translational regulation of gene expression during conditions of cell stress. Mol Cell. 2010; 40: 228-237 [OpenAIRE] [PubMed] [DOI]

Sobala, A, Hutvagner, G. Small RNAs derived from the 5' end of tRNA can inhibit protein translation in human cells. RNA Biol. 2013; 10: 553-563 [OpenAIRE] [PubMed] [DOI]

Gebetsberger, J, Zywicki, M, Kunzi, A, Polacek, N. tRNA-derived fragments target the ribosome and function as regulatory non-coding RNA in Haloferax volcanii. Archaea. 2012; 2012: 260909 [OpenAIRE] [PubMed] [DOI]

Khan, MA. Mutation in NSUN2, which Encodes an RNA Methyltransferase, Causes Autosomal-Recessive Intellectual Disability. Am J Hum Genet. 2012; 90: 856-863 [OpenAIRE] [PubMed] [DOI]

Martinez, FJ. Whole exome sequencing identifies a splicing mutation in NSUN2 as a cause of a Dubowitz-like syndrome. J Med Genet. 2012; 49: 380-385 [OpenAIRE] [PubMed] [DOI]

Abbasi-Moheb, L. Mutations in NSUN2 cause autosomal-recessive intellectual disability. Am J Hum Genet. 2012; 90: 847-855 [OpenAIRE] [PubMed] [DOI]

Blanco, S. The RNA-methyltransferase Misu (NSun2) poises epidermal stem cells to differentiate. PLoS Genet. 2011; 7: e1002403 [OpenAIRE] [PubMed] [DOI]

Hussain, S. The Mouse Cytosine-5 RNA Methyltransferase NSun2 Is a Component of the Chromatoid Body and Required for Testis Differentiation. Mol Cell Biol. 2013; 33: 1561-1570 [OpenAIRE] [PubMed] [DOI]

Fuchs, E. Cell biology: More than skin deep. J Cell Biol. 2015; 209: 629-631 [OpenAIRE] [PubMed] [DOI]

Plikus, MV, Chuong, CM. Macroenvironmental regulation of hair cycling and collective regenerative behavior. Cold Spring Harbor perspectives in medicine. 2014; 4: a015198 [OpenAIRE] [PubMed] [DOI]

Muller-Rover, S. A comprehensive guide for the accurate classification of murine hair follicles in distinct hair cycle stages. J Invest Dermatol. 2001; 117: 3-15 [OpenAIRE] [PubMed] [DOI]

70 references, page 1 of 5
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