FMRP dependent synaptic delivery of messenger RNA

Fragile X Syndrome;Fragile X Mental Retardation Protein (FMRP);mRNA targeting

Kao, Der-I

关键词: Fragile X Syndrome;    Fragile X Mental Retardation Protein (FMRP);    mRNA targeting;   

Others  :  https://www.ideals.illinois.edu/bitstream/handle/2142/18643/Kao_Der-I.pdf?sequence=1&isAllowed=y

美国|英语

来源: The Illinois Digital Environment for Access to Learning and Scholarship

【 摘 要 】

Fragile X mental retardation is the most common inherited form of mental retardation. The loss of FMRP function results in Fragile X Mental Retardation. In this dissertation, I investigated the regulatory role of FMRP involved in synaptic mRNA delivery.In chapter 1, the molecular mechanism of local protein synthesis and synaptic mRNA delivery and its roles in Fragile X syndrome and learning and memory are introduced. In chapter 2, my data demonstrated that FMRP can facilitate mRNA deceleration and localization in dendritic spines upon neurotransmitter stimulation. Consistent with these findings, local protein synthesis was also enhanced in dendritic spines after stimulation. These results suggested that FMRP could mediate synaptic mRNA delivery for local protein synthesis. In Chapter 3, the role of FMRP splicing isoforms in synaptic mRNA delivery was investigated. My data suggested phosphorylation regulation and multiple isoforms of FMRP will be required to restore mRNA targeting to dendritic spines.In conclusion, synaptic mRNA delivery regulated by FMRP isoforms was demonstrated as a novel mechanism underlying altered cognitive deficits associated with Fragile X Syndrome. When mRNA cannot be targeted properly for translation, it may result in deficits in spine structure and neurological phenotypes, such as Fragile X Syndrome. My research also corroborates the importance of spatial accuracy of protein synthesis at a microscopic level in the nervous system.