title: Increasing the Coding Potential of Genomes Through Alternative Splicing: The Case of PARK2 Gene.
abstract: The completion of the Human Genome Project aroused renewed interest in alternative splicing, an efficient and widespread mechanism that generates multiple protein isoforms from individual genes. Although our knowledge about alternative splicing is growing exponentially, its real impact on cellular life is still to be clarified. Connecting all splicing features (genes, splice transcripts, isoforms, and relative functions) may be useful to resolve this tangle. Herein, we will start from the case of a single gene, Parkinson protein 2, E3 ubiquitin protein ligase (PARK2), one of the largest in our genome. This gene is implicated in the pathogenesis of autosomal recessive juvenile Parkinsonism and it has been recently linked to cancer, leprosy, autism, type 2 diabetes mellitus and Alzheimer's disease. PARK2 primary transcript undergoes an extensive alternative splicing, which enhances transcriptomic diversification and protein diversity in tissues and cells. This review will provide an update of all human PARK2 alternative splice transcripts and isoforms presently known, and correlate them to those in rat and mouse, two common animal models for studying human disease genes. Alternative splicing relies upon a complex process that could be easily altered by both cis and trans-acting mutations. Although the contribution of PARK2 splicing in human disease remains to be fully explored, some evidences show disruption of this versatile form of genetic regulation may have pathological consequences.
authors: 1Functional Genomics Center, Institute of Neurological Sciences, Italian National Research Council, Via Paolo Gaifami 18, 95125, Catania, Italy.
authors: Valentina
authors: V
authors: La Cognata
authors: 1Functional Genomics Center, Institute of Neurological Sciences, Italian National Research Council, Via Paolo Gaifami 18, 95125, Catania, Italy.
authors: Rosario
authors: R
authors: Iemmolo
authors: 2Department of Bio-Medical Sciences, Section of Anatomy and Histology, University of Catania, Italy.
authors: Velia
authors: V
authors: D'Agata
authors: 2Department of Bio-Medical Sciences, Section of Anatomy and Histology, University of Catania, Italy.
authors: Soraya
authors: S
authors: Scuderi
authors: 3Department of Clinical and Molecular Biomedicine, Section of Pharmacology and Biochemistry, University of Catania, Italy.
authors: Filippo
authors: F
authors: Drago
authors: 4Department "G.F. Ingrassia", Section of Neuroscience, University of Catania, Italy.
authors: Mario
authors: M
authors: Zappia
authors: 1Functional Genomics Center, Institute of Neurological Sciences, Italian National Research Council, Via Paolo Gaifami 18, 95125, Catania, Italy.
authors: Sebastiano
authors: S
authors: Cavallaro
keywords: Alternative splicing; PARK2; Protein isoforms; Splice expression patterns.; Splice variants; mRNA