The Role of Alternative Splicing During the Cell Cycle and Programmed Cell Death

Publisher Summary This chapter focuses on the regulation and the influence of splicing on two important cellular processes: programmed cell death (apoptosis) and cell cycle control. Apoptosis is a process that removes deleterious or useless cells during animal development and is one of many cellular processes in which alternative splicing plays an important regulatory role. Oligonucleosomal DNA fragmentation is one of the hallmarks of apoptotic cell death. The cell cycle is a collection of highly ordered processes that lead to the duplication of a cell. Specific splicing factors are required for cell cycle progression by modulating splicing of transcripts encoding cell cycle regulators. In metazoan organisms, most transcripts synthesized by RNA polymerase (RNAP) II contain non-coding intervening sequences called introns, which must be accurately and efficiently removed by the process of pre-mRNA splicing to form translatable mRNAs. Alternative splicing is the removal of introns in different combinations. It produces diverse mature mRNAs encoding structurally and functionally distinct protein isoforms from a single gene. Alternative splicing is widely involved in gene expression in higher eukaryotes, especially in vertebrates. Pre-mRNA splicing takes place within a large molecular complex, the spliceosome, that is composed of five small nuclear RNA and a large number of protein factors. Regulation of alternative splicing largely relies on a broad spectrum of interactions between sequence elements in the mRNA precursor and a complex repertoire of protein factors. Shifting the balance between alternatively spliced isoforms of a given pre-mRNA is important in modulating both programmed cell death (apoptosis) and cell cycle control.