Alternative splicing and cell survival: from tissue homeostasis to disease.
Most human genes encode multiple mRNA variants and protein products through alternative splicing of exons and introns during pre-mRNA processing. In this way, alternative splicing amplifies enormously the coding potential of the human genome and represents a powerful evolutionary resource. Nonetheless, the plasticity of its regulation is prone to errors and defective splicing underlies a large number of inherited and sporadic diseases, including cancer. One key cellular process affected by alternative splicing is the programmed cell death or apoptosis. Many apoptotic genes encode for splice variants having opposite roles in cell survival. This regulation modulates cell and tissue homeostasis and is implicated in both developmental and pathological processes. Furthermore, recent evidence has also unveiled splicing-mediated regulation of genes involved in autophagy, another essential process for tissue homeostasis. In this review, we highlight some of the best-known examples of alternative splicing events involved in cell survival. Emphasis is given to the role of this regulation in human cancer and in the response to chemotherapy, providing examples of how alternative splicing of apoptotic genes can be exploited therapeutically.
Department of Movement, Human and Health Sciences, University of Rome 'Foro Italico', Rome 00135, Italy.|Laboratories of Cellular and Molecular Neurobiology and of Neuroembryology, Fondazione Santa Lucia, Rome 00143, Italy.
Maria Paola
MP
Paronetto
Laboratories of Cellular and Molecular Neurobiology and of Neuroembryology, Fondazione Santa Lucia, Rome 00143, Italy.|Department of Biomedicine and Prevention, University of Rome 'Tor Vergata', Rome, Italy.
Ilaria
I
Passacantilli
Laboratories of Cellular and Molecular Neurobiology and of Neuroembryology, Fondazione Santa Lucia, Rome 00143, Italy.|Department of Biomedicine and Prevention, University of Rome 'Tor Vergata', Rome, Italy.
Claudio
0000-0003-2864-8266
C
Sette
D017398:Alternative Splicing / Q000235:genetics*; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D004194:Disease / Q000235:genetics*; D006706:Homeostasis; D006801:Humans; D009369:Neoplasms / Q000235:genetics / Q000473:pathology
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