Department of Cell Biology and Biochemistry, Texas Tech University Health Sciences Center, Lubbock, TX 79430-6540, USA.
Wiley Interdiscip Rev RNA. 2010 Nov-Dec;1(3):494-501. doi: 10.1002/wrna.29.
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.
改变 mRNA 中 poly(A) 尾的位置——可变多聚腺苷酸化——是增加基因表达多样性的重要机制，尤其是在后生动物中。可变多聚腺苷酸化通常以组织或发育阶段特异性的方式发生，通过改变产生的蛋白质产物、转录本的稳定性、定位或翻译能力，显著影响基因活性。尽管可变多聚腺苷酸化对基因表达有重要的调节作用，但只有极少数例子被从机制上进行了表征。在这里，我们回顾了控制可变多聚腺苷酸化的已知机制，列出了表现出可变多聚腺苷酸化倾向的组织，并重点介绍了已知在特定组织中调节可变多聚腺苷酸化的蛋白质。我们得出的结论是，可变多聚腺苷酸化领域仍处于起步阶段，未来还有更多的研究可能性。鉴于可变多聚腺苷酸化对基因表达和人类健康可能产生的深远影响，对可变多聚腺苷酸化的深入了解可能会导致对基因活性控制的许多进展。
