Alternative cleavage and polyadenylation in human CD46

Abstract

Although well-known as a negative regulator of complement activation, human transmembrane protein CD46 plays multiple roles in immunity and immune-independent processes. Various mechanisms, including alternative splicing and posttranslational modifications, contribute to the CD46’s multitasking through generating isoforms with distinct functions. However, the role of Alternative Polyadenylation (APA), by which a gene creates various transcripts different either in their 3’ untranslated region (3’UTR) or Open Reading Frame (ORF), is yet unestablished for CD46. In this study, we aimed to characterize APA in CD46, focusing on APA occurring in introns or the 3’ terminal exon. To achieve this goal, we exploited the properties of APA-generated mRNAs such as intronic retention in mRNAs, the responsiveness to functional U1 levels of intronically terminated transcripts, and we performed 3’RACE to detect alternatively polyadenylated mRNAs. By the end of this study, we have successfully demonstrated that CD46 undergoes multiple types of APA, by which various truncated mRNAs altered either in their ORFs or 3’UTRs are generated. These results ultimately underscore the potential of APA as an essential mechanism to regulate CD46 expression and function.