Alternative Splicing Expression Of FMR1 Gene

Fragile X syndrome is the most common cause of inherited mental retardation, associated with a fragile site at Xq27.3. In 1991, the FMRl gene, the mutation of which is considered the cause of fragile X syndrome, was cloned in this region.High level expression of FMRl gene has been observed throughout the embryo, as well as the brain and testis of adult. Low level expression of FMRl gene was also documented in most of the adult tissues. FMR1 seems to be a house keeping gene, essential to the normal functions of the cells. It also likely plays an important role during the development of central nervous system. FMRl gene encoded an RNA-bind protein, FMRP, which binds to ribosome via RNA. Thus, FMRP may be a translation regulator.Four exons of FMR1 gene was observed that can be alternatively spliced. Coexistent of different alternative splicing variants of FMR1 gene has been detected in many tissues, both at mRNA and protein levels. It is difficult to distinguish the different alternative splicing variants by conventional methods, as the regions involve in alternative splicing is relatively large, and there is only slightly difference between different splicing variants. Further more, there are no splicing variants specific antibodies available. At present, it is still elusive that when, where and which splicing variants express, in different tissues.In the works described here, a 'colonization' strategy was used to analyze the alternative splicing expression of FMR1 gene at mRNA level. Complex alternative splicing of FMR1 gene was detected in cultured human fetal brain neuron, and 11 different splicing isoforms were cloned. The relative abundance of different...