Alternative splicing is an important mechanism for generating transcript and protein diversity. In the brain, alternative splicing is particularly prevalent, and alternative splicing factors are highly enriched. These include the six members of the CUG-BP, Elav-like family (CELF). This review summarizes what is known about the expression of different CELF proteins in the nervous system and the evidence that they are important in neural development and function. The involvement of CELF proteins in the pathogenesis of a number of neurodegenerative disorders, including myotonic dystrophy, spinocerebellar ataxia, fragile X syndrome, spinal muscular atrophy, and spinal and bulbar muscular atrophy is discussed. Finally, the known targets of CELF-mediated alternative splicing regulation in the nervous system and the functional consequences of these splicing events are reviewed. This article is part of a Special Issue entitled "RNA and splicing regulation in neurodegeneration."
Keywords: APP; Alternative splicing; Amyloid precursor protein; Brain; CELF; CLIP; CUG-BP, Elav-like family; Crosslinking immunoprecipitation; DM1; GABT4; Gamma-aminobutyric acid transporter 4; MAPT; MBNL; Microtubule-associated protein tau; Muscle blind-like; Myotonic dystrophy; Myotonic dystrophy type 1; N-methyl-d-aspartate receptor 1; NF1; NMDAR1; Neurofibromin 1; Neurological disorders; Neurons; SBMA; SCA; SMA; SMN; Spinal and bulbar muscular atrophy; Spinal muscular atrophy; Spinocerebellar ataxia; Survival motor neuron.
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