Stem cell function and stress response are controlled by protein synthesis

Article

关键词: OPEN READING FRAMES;    METHYLTRANSFERASE MISU NSUN2;    RNA METHYLTRANSFERASE;    GENE-EXPRESSION;    MESSENGER-RNA;    TRANSLATIONAL REGULATION;    TGF-BETA;    IN-VIVO;    METHYLATION;    IDENTIFICATION;   

DOI  :  10.1038/nature18282

来源: SCIE

【 摘 要 】

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 inhibition renders stem cells hypersensitive to cytotoxic stress, as tumour regeneration after treatment with 5-fluorouracil is blocked. Thus, stem cells must revoke translation inhibition pathways to regenerate a tissue or tumour.

【 授权许可】

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