A difference in the splicing patterns of the closely related normal and variant human growth hormone gene transcripts is determined by a minimal sequence divergence between two potential splice-acceptor sites.
The human growth hormone (hGH-N) and the closely related human growth hormone-variant (hGH-V) genes differ in their patterns of splice-site selection. In 9% of hGH-N transcripts exon 2 is spliced to an alternative acceptor site located 45 bases within exon 3. mRNA spliced in this manner encodes a 20-kDa hGH-N isoform instead of the normal 22-kDa hGH-N. The hGH-V transcript fails to utilize this alternative splicing pathway. A region of the hGH-N and hGH-V genes critical to this difference in splice-site selection has been identified by reciprocal exchange of corresponding genomic fragments and has been defined in detail by a series of reciprocal site-specific exchanges. Three base differences located between the two potential splice-acceptor sites are both necessary and sufficient in defining the respective splicing patterns. One of these bases may serve as a lariat branch point critical for the alternative acceptor site activity while the remaining two bases appear to modulate the frequency with which this site is selected.
Estes
P A
PA
Howard Hughes Medical Institute, University of Pennsylvania, Philadelphia 19104.
Cooke
N E
NE
Liebhaber
S A
SA
D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D004262:DNA Restriction Enzymes; D005091:Exons; D014644:Genetic Variation; D013006:Growth Hormone / Q000235:genetics*; D006801:Humans; D051379:Mice; D016297:Mutagenesis, Site-Directed; D010957:Plasmids; D012326:RNA Splicing / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D014158:Transcription, Genetic
D012333:RNA, Messenger; D013006:Growth Hormone; D004262:DNA Restriction Enzymes