The implications of alternative pre-mRNA splicing in cell signal transduction

Abstract

Cells produce multiple mRNAs through alternative splicing, which ensures proteome diversity. Because most human genes undergo alternative splicing, key components of signal transduction pathways are no exception. Cells regulate various signal transduction pathways, including those associated with cell proliferation, development, differentiation, migration, and apoptosis. Since proteins produced through alternative splicing can exhibit diverse biological functions, splicing regulatory mechanisms affect all signal transduction pathways. Studies have demonstrated that proteins generated by the selective combination of exons encoding important domains can enhance or attenuate signal transduction and can stably and precisely regulate various signal transduction pathways. However, aberrant splicing regulation via genetic mutation or abnormal expression of splicing factors negatively affects signal transduction pathways and is associated with the onset and progression of various diseases, including cancer. In this review, we describe the effects of alternative splicing regulation on major signal transduction pathways and highlight the significance of alternative splicing.

Molecular genetics: RNA splicing in health and disease

Cell signaling processes are affected by the varying ways that sections of messenger RNA (mRNA), the molecule that carries genetic instructions copied from a gene, are spliced together to generate several different proteins from a single gene. Kee K. Kim and colleagues at Chungnam National University in Daejon, South Korea, review the significance for cell signaling of the alternative splicing patterns of mRNAs. Mutations that lead to the splicing processes going awry are implicated in a range of diseases, including cancer. The authors examine the most recent research insights gained by applying emerging methods of genetic analysis to the role of mRNA splicing in several specific cell signaling pathways vital for normal development and health. They suggest that increasing understanding of faulty splicing in disease could open avenues towards new forms of treatment.