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Publication : The P-body protein 4E-T represses translation to regulate the balance between cell genesis and establishment of the postnatal NSC pool.

First Author  Kolaj A Year  2023
Journal  Cell Rep Volume  42
Issue  3 Pages  112242
PubMed ID  36924490 Mgi Jnum  J:334886
Mgi Id  MGI:7463828 Doi  10.1016/j.celrep.2023.112242
Citation  Kolaj A, et al. (2023) The P-body protein 4E-T represses translation to regulate the balance between cell genesis and establishment of the postnatal NSC pool. Cell Rep 42(3):112242
abstractText  Here, we ask how developing precursors maintain the balance between cell genesis for tissue growth and establishment of adult stem cell pools, focusing on postnatal forebrain neural precursor cells (NPCs). We show that these NPCs are transcriptionally primed to differentiate and that the primed mRNAs are associated with the translational repressor 4E-T. 4E-T also broadly associates with other NPC mRNAs encoding transcriptional regulators, and these are preferentially depleted from ribosomes, consistent with repression. By contrast, a second translational regulator, Cpeb4, associates with diverse target mRNAs that are largely ribosome associated. The 4E-T-dependent mRNA association is functionally important because 4E-T knockdown or conditional knockout derepresses proneurogenic mRNA translation and perturbs maintenance versus differentiation of early postnatal NPCs in culture and in vivo. Thus, early postnatal NPCs are primed to differentiate, and 4E-T regulates the balance between cell genesis and stem cell expansion by sequestering and repressing mRNAs encoding transcriptional regulators.
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