Obiettivo
Alternative splicing is the process by which multiple mRNA isoforms can be generated from one gene by differential usage of alternative exons in the mature mRNA. It is a major mechanism by which higher vertebrates generate functional complexity of their proteome. Approximately 95% of human genes are alternatively spliced and this process is especially abundant in the nervous system and crucial for proper regulation of neuronal gene expression. Evidence comes from identification of mutations disrupting pre-mRNA sequences, required for alternative splicing, but not for protein coding that cause neurological disease in humans. Moreover, mutations of some RNA binding proteins, with roles in alternative mRNA processing, also result in neuro-developmental disorders and widespread misregulation of alternative splicing. With advancements of high throughput sequencing techniques our knowledge about the kinds of alternative mRNA isoforms and their abundance in different kinds of tissue is rapidly increasing. However, our understanding of the functional consequences of neuron-specific alternative splicing is still very limited. During my postdoctoral studies I have discovered that Hu RNA binding proteins are required for alternative splicing of pre-mRNA targets with important roles in neuronal development and function. I propose to investigate the functions of individual protein isoforms that are translated from Hu-dependent alternative mRNA isoforms. Initially I will focus on studying the functions of the isoforms of the Kif2a gene, which encodes a kinesin motor protein involved in neuronal cytoskeleton dynamics and intracellular cargo transport. I will especially focus on understanding how Kif2a isoforms regulate development of axons and also the transport of cargo to neuronal processes. I believe that my studies will contribute to our knowledge of how neuronal development and physiology is regulated by alternative splicing.
Campo scientifico
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FP7-PEOPLE-2010-RG
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Meccanismo di finanziamento
MC-IRG - International Re-integration Grants (IRG)Coordinatore
34450 Istanbul
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