Stem-cell function and stress response are controlled at protein synthesis level

This report [attached] describes interesting research on a unique idea: Are the functions of embryonic stem (ES) cells controlled at the level of transcription (DNA –> RNA) or at the level of translation (RNA –> protein)? And does the “stress response” pathway in these cells play any role?

Whether protein synthesis and cellular stress response pathways interact to control ES cell functions is currently unknown. Authors show [attached] that mouse skin ES cells synthesize less protein than their immediate progenitors in vivo, even when forced to divide rapidly (proliferate). The analyses of the authors reveal that activation of stress response pathways drives both a global decline in protein synthesis and altered translational programs––that together promote ES cell functions and tumorigenesis.

Mechanistically, authors show that inhibition of post-transcriptional cytosine-5 methylation locks tumor-initiating cells into this distinct translational inhibition program. Paradoxically, this inhibition renders ES cells hypersensitive to cytotoxic stress, because tumor regeneration after treatment with 5-fluorouracil is blocked. Therefore, ES cells must revoke translation inhibition pathways––in order to regenerate a tissue or tumor.

Nature  16 June 2016; 534: 335–340

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