Alternative polyadenylation (APA) is how genes choose different sites for 3' end formation for mRNAs during transcription. APA often occurs in a tissue- or developmental stage-specific manner that can significantly affect gene activity by changing the protein product generated, the stability of the transcript, its localization within the cell, or its translatability. Despite the important regulatory effects that APA has on tissue-specific gene expression, only a few examples have been characterized mechanistically. In this 2018 update to our 2010 review, we examine mechanisms for the control of APA and update our understanding of the older mechanisms since 2010. We once postulated the existence of tissue-specific factors in APA. However, while a few tissue-specific polyadenylation factors are known, the emerging conclusion is that the majority of APA is accomplished by altering levels of core polyadenylation proteins. Examples of those core proteins include CSTF2, CPSF1, and subunits of mammalian cleavage factor I. But despite support for these mechanisms, no one has yet documented any of these proteins changing in either a tissue-specific or developmental manner. Given the profound effect that APA can have on gene expression and human health, improved understanding of tissue-specific APA could lead to numerous advances in gene activity control. This article is categorized under: RNA Processing > 3' End Processing RNA in Disease and Development > RNA in Development.

中文翻译：

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替代性聚腺苷酸化的组织特异性机制：睾丸，大脑及其他（2018年更新）。

替代性聚腺苷酸化（APA）是基因如何在转录过程中选择不同的位点来为mRNA的3'端形成。APA通常以组织或发育阶段特定的方式发生，可通过改变生成的蛋白质产物，转录本的稳定性，其在细胞内的位置或可翻译性来显着影响基因活性。尽管APA对组织特异性基因表达具有重要的调节作用，但仅通过机械方法鉴定了几个例子。在我们对2010年回顾的2018年更新中，我们研究了APA控制机制，并更新了我们自2010年以来对较旧机制的理解。我们曾经假设APA中存在组织特异性因子。但是，虽然已知一些组织特异性的聚腺苷酸化因子，新出现的结论是，大多数APA是通过改变核心多腺苷酸化蛋白的水平来实现的。这些核心蛋白的例子包括CSTF2，CPSF1和哺乳动物切割因子I的亚基。但是，尽管支持这些机制，但尚无人证明这些蛋白以组织特异性或发育方式发生变化。鉴于APA可以对基因表达和人类健康产生深远的影响，对组织特异性APA的更好理解可能会导致基因活性控制方面的许多进步。本文归类于：RNA加工> 3'末端加工RNA在疾病与发育中> RNA在发育中。尽管有这些机制的支持，但尚无人证明这些蛋白质以组织特异性或发育方式发生变化。鉴于APA可以对基因表达和人类健康产生深远的影响，对组织特异性APA的更好理解可能会导致基因活性控制方面的许多进步。本文归类于：RNA加工> 3'末端加工RNA在疾病与发育中> RNA在发育中。尽管有这些机制的支持，但尚无人证明这些蛋白质以组织特异性或发育方式发生变化。鉴于APA可以对基因表达和人类健康产生深远的影响，对组织特异性APA的更好理解可能会导致基因活性控制方面的许多进步。本文归类于：RNA加工> 3'末端加工RNA在疾病与发育中> RNA在发育中。