Zhu, H: a New Journey Of Hu Protein Family

Alternative splicing is a general mechanism in higher eukaryotic organisms to increase their diversity. In contrast to its importance, the mechanism of alternative splicing regulation is poorly understood, especially in the nervous system, where extensive alternative splicing occurs. During my Ph.D. study, I identified a family of novel neuron-specific splicing regulators, Hu proteins. My studies provided solid evidence that support the splicing regulatory function of Hu proteins. Two genes that undergo neuron-specific splicing were used as model in my research: calcitonin/CGRP and NF1. In calcitonin/CGRP gene model, Hu proteins inhibit the recognition of the non-neuronal exon by two mechanisms: blocking the positive splicing factors TIA-1/R and suppressing polyadenylation. NF1 is a well-studied tumor suppressor, and the neuron-specific skipping of exon 23a has been reported to change its activity. My research demonstrated that Hu proteins strongly suppress recognition of exon 23a by the splicing machinery in neurons. In summary, my research has contributed significantly to the understanding of the splicing regulation in neurons.