EXON SKIPPING DURING SPLICING OF ALBUMIN MESSENGER-RNA PRECURSORS IN NAGASE ANALBUMINEMIC RATS

Based on the observation that albumin transcripts accumulate in the liver nuclear RNA fraction of Nagase analbuminemic rats (NAR), it was proposed [Esumi, H., Takahashi, Y., Shigeaki, S., Nagase, S. & Takahashi, S. (1983) Proc. Natl. Acad. Sci. USA 80, 95-99] that a 7-base-pair deletion at the splice donor site of intron H-I of the albumin gene in these animals leads to impaired processing of albumin pre-mRNA. To identify the specific splicing abnormality, we examined the primary structure of cytoplasmic albumin mRNA across the junctions of exons G-H-I by RNase protection mapping, Northern blot hybridization, Southern blot analysis of polymerase chain reaction-amplified cDNA, and DNA sequencing. The major albumin mRNA species in NAR showed precise deletion of exon H, suggesting that this exon was skipped during albumin pre-mRNA processing. Since the intron G-H splice donor and acceptor sites and exon H sequence are normal, the finding of exon H skipping in NAR has important implications regarding the mechanism of splice site selection. Moreover, the NAR model provides an excellent system to study splicing in vivo in a higher animal.