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.