Figure 10 of Bitel, Mol Vis 2010; 16:2301-2316.


Figure 10. Model of regulatory interactions between factors expressed in neural progenitors and lens epithelial cells versus post-mitotic neurons and lens fiber cells. In neurons REST/NRSF transcription factors, HuR-HuB/C/D and PTB-nPTB RNA binding proteins, with miR-124 form a network that differentially regulates non-neural and neuron-specific alternative splicing and gene expression. REST suppresses >1,500 neuronal genes in non-neuronal cells throughout the body. In post-mitotic neurons REST decreases, and neuron-specific alternatively spliced REST4 is produced, further relieving repression of these genes. Ubiquitous HuR and PTB that promote non-neural splicing are also replaced by neuron-specific HuB/C/D and nPTB in post-mitotic neurons, which leads to a comprehensive reprogramming of neuron-specific alternative splicing. In non-neural cells, PTB alters nPTB transcript splicing to tag them for nonsense mediated decay. In post-mitotic neurons, REST repression of miR-124 expression is alleviated, allowing miR-124 to suppress hundreds of non-neuronal transcripts, including PTB.