Figure 1.

Schematic illustration of transcription, pre-mRNA processing/splicing and translation. A protein-coding gene is transcribed by RNA polymerase II into pre-mRNA. Subsequently, or already during transcription, non-coding introns are removed in a process called splicing, after which the mature mRNA is capped and polyadenylated and transported to the cytoplasm where it is translated into protein. Depicted is a gene consisting of four exons interspersed by three introns. Under normal splicing conditions, exons 1, 3 and 4 are linked together forming the vast majority of mature transcripts (bold black arrow). Alternative splicing may recombine gene elements into new configurations that may or may not display the activity or characteristics of the original protein. For example, alternative splicing reactions (grey arrows) can result in the acquirement of an extra exon (exon 2), in the skipping of exons (exon 2 and 3) or in an extra exon and part of the first intron through the use of a cryptic splice site in the first intron. In the latter case, a truncated protein may form due to the presence of a termination codon in the remaining intron sequence. Under normal circumstances, nonsense-mediated decay (NMD) is responsible for the degradation of mRNAs that have a premature stop codon to prevent the synthesis of detrimental truncated proteins. Note that the NMD is dysfunctional in cells treated with spliceostatin A leading to the expression of truncated proteins (see text for details).