Alternative Splicing Generates Transcripts with Different Combinations of Exons

The discovery that a large fraction of transcription units in higher organisms encode alternatively spliced mRNAs and that differently spliced mRNAs are expressed in different cell types revealed that regulation of RNA splicing is an important gene-control mechanism in higher eukaryotes. Although many examples of cleavage at alternative poly(A) sites in pre-mRNAs are known, alternative splicing of different exons is the more common mechanism for expressing different proteins from one complex transcription unit. In Chapter 5, for example, we mentioned that fibroblasts produce one type of the extracellular protein fibronectin, whereas hepatocytes produce another type. Both fibronectin isoforms are encoded by the same transcription unit, but the transcript is spliced differently in the two cell types to yield two different mRNAs (see Figure 5-16). In other cases, alternative processing of the same transcript may occur simultaneously in the same cell type in response to different developmental or environmental signals. We first discuss one of the best-understood examples of regulated RNA processing, then briefly consider the consequences of RNA splicing in the development of the nervous system.