Fragile X syndrome is the most common form of hereditary intellectual disability among men, caused by the loss of function of the FMRP protein, encoded by the FMR1 gene, which has regulatory roles in the translational repression of messenger RNAs (mRNAs) involved mainly in neuronal maturation and synaptic plasticity. The segment encoded by exon 14 of FMR1 influences the cytoplasmic or nuclear distribution of the protein and this exon can undergo alternative splicing, changing the translational reading frame. On the other hand, the alternative inclusion of exon 12 significantly leads to an in-frame 21-residue extension in the KH2 domain of FMRP, in the first postnatal week, a period of active synaptogenesis. Previously, exonic and intronic elements were identified as candidates for the regulation of exons 14 and 12 splicing, respectively, as well as specific splicing proteins associated with them. This proposal aims at confirming the interaction of candidate proteins and cis-elements in exon 14 and intron 12 of FMR1 transcripts and to verify whether there is a regulatory relationship.
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