An intronic polyadenylation site in human and mouse CstF-77 genes suggests an evolutionarily conserved regulatory mechanism

Abstract

Human CstF-77 is one of the three subunits of cleavage stimulation factor (CstF) that is essential for mRNA polyadenylation. Its Drosophila homologue, suppressor of forked [su(f)], contains an intronic poly(A) site, which can lead to a short transcript without a stop codon. By both bioinformatic searches and validation with molecular biology experiments, we found that human and mouse CstF-77 genes also contain an intronic poly(A) site, which can be utilized to produce short CstF-77 transcripts lacking sequences encoding domains that are involved in many of the CstF-77 functions. The genomic sequence surrounding the poly(A) site is highly conserved among all vertebrates, but is not present in non-vertebrate species. Using public Serial Analysis of Gene Expression (SAGE) data, we found that the intronic poly(A) site is utilized in a wide range of tissues. This finding indicates that vertebrates may employ a similar alternative polyadenylation mechanism to modulate CstF-77, highlighting the importance of the regulation of CstF-77 in various species.