The RNA polymerase II subunit Rpb4p mediates decay of a specific class of mRNAs

The RNA polymerase II subunit Rpb4p mediates decay of a specific class of mRNAs
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DOI:
10.1101/gad.353205
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发表时间:
2005-12-15
影响因子:
10.5
通讯作者:
Choder, M
Choder, M
中科院分区:
生物学1区
文献类型:
--
作者:
Lotan, R;Bar-On, VG;Choder, M

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通常认为,mRNA水平由其合成和衰变动力学之间的平衡决定。然而,人们对这些不同进程之间的协调知之甚少。真核生物mRNA降解的主要途径起始于mRNA poly(A)尾的缩短(去腺苷酸化),随后是mRNA 5'帽结构的去除及其随后的核酸外切降解。在这里,我们报告的RNA聚合酶II,Rpb 4p,是需要一类mRNA的衰变,其产品参与蛋白质合成的亚基。缺乏RPB 4的细胞在这类mRNA的代表的去腺苷化和去腺苷化后步骤中有缺陷。此外,Rpb 4p与mRNP和mRNA衰变复合物Patl/Lsml-7的亚基相互作用,其增强去帽。因此,Rpb 4p的一部分定位于P小体,在那里进行mRNA去帽和降解,并且RPB 4中的突变增加了每个细胞的P小体的数量。我们提出Rpb 4p在mRNA降解中具有双重功能。它促进或增强特定mRNA的去腺苷化过程,并将Patl/Lsml-7募集到这些mRNA,从而刺激它们的去帽和进一步衰变。这样,Rpb 4p可能将基础转录器的活性与mRNA衰变机制的活性联系起来。
It is commonly appreciated that the mRNA level is determined by the balance between its synthetic and decay kinetics. Yet, little is known about coordination between these distinct processes. A major pathway of the eukaryotic mRNA decay initiates with shortening of the mRNA poly(A) tail (deadenylation), followed by removal of the mRNA 5' cap structure and its subsequent exonucleolytic degradation. Here we report that a subunit of RNA polymerase II, Rpb4p, is required for the decay of a class of mRNAs whose products are involved in protein synthesis. Cells lacking RPB4 are defective in the deadenylation and post-deadenylation steps of representatives of this class of mRNAs. Moreover, Rpb4p interacts with both the mRNP and with subunits of the mRNA decay complex Patl/Lsml-7 that enhances decapping. Consistently, a portion of Rpb4p is localized in P bodies, where mRNA decapping and degradation is executed, and mutations in RPB4 increase the number of P bodies per cell. We propose that Rpb4p has a dual function in mRNA decay. It promotes or enhances the deadenylation process of specific mRNAs and recruits Patl/Lsml-7 to these mRNAs, thus stimulating their decapping and further decay. In this way, Rpb4p might link the activity of the basal transcription apparatus with that of the mRNA decay machinery.