Fig 6. Model for Celf1-mediated post-transcriptional gene expression control in the lens.In normal lens development, Celf1 is required for nuclear degradation and proper cell morphology in fiber cell differentiation. Celf1 positively regulates the nuclease Dnase2b (being necessary for its high mRNA levels) and negatively regulates the cyclin-dependent kinase inhibitors p21Cip1 (being necessary for its low mRNA levels) and p27Kip1 (by inhibiting its translation into protein). Inhibition of p21Cip1 and p27Kip1 allows the activation of Cdk1, which phosphorylates Lamin A/C to initiate nuclear envelope breakdown in fiber cells. Thus, Celf1 controls the nuclease (Dnase2b) as well as its access to nuclear DNA, to regulate nuclear degradation in lens fiber cells. These findings show how mitotic machinery components–normally involved in nuclear envelope disassembly during cell division–are post-transcriptionally rewired by RNA-binding proteins to regulate cell differentiation in lens development. Additionally, Celf1 controls the splice isoform abundance of the membrane-organization protein Sptb (β-spectrin) and high transcript levels of the F-actin-binding protein Actn2 (α-actinin 2), to regulate fiber cell morphology. Abbr.: Epi, epithelium; TZ, transition zone; FC, fiber cells.
Image published in: Siddam AD et al. (2018)
© 2018 Siddam et al. This image is reproduced with permission of the journal and the copyright holder. This is an open-access article distributed under the terms of the Creative Commons Attribution license
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