An active role for splicing in 3′-end formation
An active role for splicing in 3′-end formation
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DOI：
10.1002/wrna.68
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发表时间：
2011-07-01
影响因子：
7.3
通讯作者：
Martinson, Harold G.
中科院分区：
文献类型：
--
作者：
Martinson, Harold G.
在高等真核生物的进化中，当内含子定义的剪接被外显子定义的剪接所取代时，剪接装置不得不依赖于切割/聚腺苷酸化（CP）装置来帮助定义3'端外显子。由此产生的3‘端外显子定义复合物由上游3’剪接位点（ss）上的剪接因子与下游poly(A)信号上的CP因子相互作用组成。这个加工复合体的推测模型提出了几个离散的步骤。首先，剪接因子U2AF65与CP因子CFIm相互作用。然后，在重塑过程中，CFIm被聚(A)聚合酶从U2AF65中置换。最后，U2 snRNP与CPSF相互作用的步骤类似于剪接体a复合体的形成。结果是外显子的剪接和CP相互增强。相反，当poly(A)信号之前是5‘而不是3’ s时，竞争取代了合作。因此，内含子中的poly(a)位点必须与上游的5’s位点竞争，才能与更上游的3’s位点配对，穿过假定的外显子。如果poly(A)位点赢得竞争，则定义终端外显子。但是如果5' s胜出（通过将上游外显子定义为内部，然后与下游内含子的3' s配对），那么poly(a)位点被抑制。U1 snRNP通过其在剪接位点配对中的作用明显参与了这种竞争。然而，除了剪接位点外，U1 snRNP还可以结合转录本的其他位置，通过与CP因子的直接相互作用来调节CP。(C) 2010 John Wiley & Sons, Ltd。WIREs RNA 2011 2 459-470 DOI: 10.1002/wrna.68
When intron-defined splicing was replaced by exon-defined splicing in the evolution of higher eukaryotes, the splicing apparatus had to rely on the cleavage/polyadenylation (CP) apparatus for help in defining the 3'-terminal exon. The 3'-terminal exon-definition complex that resulted consists of splicing factors on the upstream 3' splice site (ss) interacting with CP factors on the downstream poly(A) signal. A speculative model for assembly of this processing complex proposes several discrete steps. First, the splicing factor, U2AF65, interacts with the CP factor, CFIm. Then, CFIm is displaced from U2AF65 by the poly(A) polymerase during a remodeling step. Finally, the U2 snRNP interacts with CPSF in a step resembling spliceosomal A-complex formation. The result is mutual enhancement of both splicing and CP for the exon. In contrast, when the poly(A) signal is preceded by a 5' rather than a 3' ss, competition replaces cooperation. Thus, a poly(A) site in an intron must compete with the upstream 5' ss for pairing with the 3' ss further upstream, across the presumptive exon. If the poly(A) site wins the competition, a terminal exon is defined. But if the 5' ss wins (by defining the upstream exon as internal, followed by pairing with a 3' ss across the downstream intron), then the poly(A) site is suppressed. The U1 snRNP obviously participates in this competition through its role in splice site pairing. However, the U1 snRNP can also bind elsewhere in the transcript, apart from splice sites, to regulate CP by direct interaction with the CP factors. (C) 2010 John Wiley & Sons, Ltd. WIREs RNA 2011 2 459-470 DOI: 10.1002/wrna.68