Alternative splicing caused by RNA secondary structure.

mRNA precursors with stable hairpins were constructed by inserting inverted repeats into an adenovirus transcriptional template that encoded the three late leader exons. When the loop of the hairpin contained the second exon and the flanking splice sites, most of the RNA spliced in vitro had the first exon joined directly to the third exon. The remainder was spliced normally. The same types of alternatively spliced RNAs were formed when a similar template was introduced into HeLa cells by transfection. Thus both in extracts and in cells, an exon became optional when sequestered in a hairpin loop. Perhaps a related mechanism creates the alternative splicing patterns of complex transcription units.