Max-Planck-Institute of Molecular Cell Biology and Genetics, Dresden, Germany.
Wiley Interdiscip Rev RNA. 2011 May-Jun;2(3):348-61. doi: 10.1002/wrna.56. Epub 2010 Nov 17.
Poly(A) tails have long been known as stable 3' modifications of eukaryotic mRNAs, added during nuclear pre-mRNA processing. It is now appreciated that this modification is much more diverse: A whole new family of poly(A) polymerases has been discovered, and poly(A) tails occur as transient destabilizing additions to a wide range of different RNA substrates. We review the field from the perspective of poly(A) tail length. Length control is important because (1) poly(A) tail shortening from a defined starting point acts as a timer of mRNA stability, (2) changes in poly(A) tail length are used for the purpose of translational regulation, and (3) length may be the key feature distinguishing between the stabilizing poly(A) tails of mRNAs and the destabilizing oligo(A) tails of different unstable RNAs. The mechanism of length control during nuclear processing of pre-mRNAs is relatively well understood and is based on the changes in the processivity of poly(A) polymerase induced by two RNA-binding proteins. Developmentally regulated poly(A) tail extension also generates defined tails; however, although many of the proteins responsible are known, the reaction is not understood mechanistically. Finally, destabilizing oligoadenylation does not appear to have inherent length control. Rather, average tail length results from the balance between polyadenylation and deadenylation.
聚(A)尾长期以来一直被认为是真核 mRNA 的稳定 3' 修饰,在核前体 mRNA 加工过程中添加。现在人们认识到这种修饰要多样化得多:已经发现了一整套新的聚(A)聚合酶家族,并且聚(A)尾作为不稳定的添加物出现在广泛的不同 RNA 底物上。我们从聚(A)尾长度的角度来回顾这个领域。长度控制很重要,因为 (1) 从定义的起点开始缩短 poly(A) 尾会作为 mRNA 稳定性的计时器,(2) poly(A) 尾长度的变化用于翻译调控目的,以及 (3) 长度可能是区分 mRNA 的稳定 poly(A) 尾和不同不稳定 RNA 的不稳定 oligo(A) 尾的关键特征。核前体 mRNA 加工过程中的长度控制机制相对较为清楚,基于两种 RNA 结合蛋白诱导的聚(A)聚合酶的持续性变化。发育调控的 poly(A) 尾延伸也会产生特定的尾长;然而,尽管已知许多负责的蛋白质,但该反应的机制尚不清楚。最后,不稳定的寡聚腺苷酸化似乎没有固有的长度控制。相反,平均尾长是由聚腺苷酸化和去腺苷酸化之间的平衡决定的。