Exon skipping during splicing of albumin mRNA precursors in Nagase analbuminemic rats

Abstract

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.