mRNA alternative polyadenylation (APA) in regulation of gene expression and diseases

Abstract The mRNA polyadenylation plays essential function in regulation of mRNA metabolism. Mis-regulations of mRNA polyadenylation are frequently linked with aberrant gene expression and diseases progression. Under the action of polyadenylate polymerase, poly(A) tail is synthesized after the polyadenylation signal (PAS) sites on the mRNAs. Alternative polyadenylation (APA) often occurs in mRNAs with multiple poly(A) sites, producing transcription variants different 3'ends, and therefore plays important function on gene expression regulation. In this review, we first summarize the classical process of mRNA 3'-terminal formation and discuss the length control mechanisms of poly(A) in nucleus and cytoplasm. Then we review the research progress on alternative polyadenylation regulation and the APA site selection mechanism. Finally, we summarize functional role of APA in regulation of gene expression and diseases including cancers.