GLD-4-Mediated Translational Activation Regulates the Size of the Proliferative Germ Cell Pool in the Adult Germ Line
Throughout adulthood, animal tissue homeostasis requires adult stem cell activities. A tight balance between self-renewal and differentiation protects against tissue overgrowth or loss. This balance is strongly influenced by niche-mediated signaling pathways that primarily trigger a transcriptional response in stem cells to promote self-renewal/proliferation. However, the cell-intrinsic mechanisms that modulate signaling pathways to promote proliferation or differentiation are poorly understood. Recently, post-transcriptional mRNA regulation emerged in diverse germline stem cell systems as an important gene expression mechanism, primarily preventing the protein synthesis of factors that promote the switch to differentiation. In the adult C. elegans germ line, this study finds that the evolutionarily conserved cytoplasmic poly(A) polymerase, GLD-4, plays an crucial role in maintaining a healthy balance between proliferation and differentiation forces. This is in part due to translational activation of the mRNA that encodes the germ cell-expressed Notch signaling receptor, an essential regulator of proliferation. Moreover, GLD-4 activity is part of a redundant genetic network downstream of Notch that, together with several other conserved mRNA regulators, promotes differentiation onset. Given the widespread expression of these conserved RNA regulators in metazoans, cell fate balances that are reinforced by translational activation and repression circuitries may therefore be a general mechanism of adult tissue maintenance.
Vyšlo v časopise:
GLD-4-Mediated Translational Activation Regulates the Size of the Proliferative Germ Cell Pool in the Adult Germ Line. PLoS Genet 10(9): e32767. doi:10.1371/journal.pgen.1004647
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pgen.1004647
Souhrn
Throughout adulthood, animal tissue homeostasis requires adult stem cell activities. A tight balance between self-renewal and differentiation protects against tissue overgrowth or loss. This balance is strongly influenced by niche-mediated signaling pathways that primarily trigger a transcriptional response in stem cells to promote self-renewal/proliferation. However, the cell-intrinsic mechanisms that modulate signaling pathways to promote proliferation or differentiation are poorly understood. Recently, post-transcriptional mRNA regulation emerged in diverse germline stem cell systems as an important gene expression mechanism, primarily preventing the protein synthesis of factors that promote the switch to differentiation. In the adult C. elegans germ line, this study finds that the evolutionarily conserved cytoplasmic poly(A) polymerase, GLD-4, plays an crucial role in maintaining a healthy balance between proliferation and differentiation forces. This is in part due to translational activation of the mRNA that encodes the germ cell-expressed Notch signaling receptor, an essential regulator of proliferation. Moreover, GLD-4 activity is part of a redundant genetic network downstream of Notch that, together with several other conserved mRNA regulators, promotes differentiation onset. Given the widespread expression of these conserved RNA regulators in metazoans, cell fate balances that are reinforced by translational activation and repression circuitries may therefore be a general mechanism of adult tissue maintenance.
Zdroje
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Štítky
Genetika Reprodukčná medicínaČlánok vyšiel v časopise
PLOS Genetics
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