Tissue-specific mechanisms of alternative polyadenylation: Testis, brain, and beyond

Changing the position of the poly(A) tail in an mRNA-alternative polyadenylation-is an important mechanism to increase the diversity of gene expression, especially in metazoans. Alternative polyadenylation often occurs in a tissue- or developmental stage-specific manner and can significantly affect gene activity by changing the protein product generated, the stability of the transcript, its localization, or its translatability. Despite the important regulatory effects that alternative polyadenylation have on gene expression, only a sparse few examples have been mechanistically characterized. Here, we review the known mechanisms for the control of alternative polyadenylation, catalog the tissues that demonstrate a propensity for alternative polyadenylation, and focus on the proteins that are known to regulate alternative polyadenylation in specific tissues. We conclude that the field of alternative polyadenylation remains in its infancy, with possibilities for future investigation on the horizon. Given the profound effect alternative polyadenylation can have on gene expression and human health, improved understanding of alternative polyadenylation could lead to numerous advances in control of gene activity.