A splicing-dependent transcriptional checkpoint associated with prespliceosome formation.
A splicing-dependent transcriptional checkpoint associated with prespliceosome formation.
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DOI：
10.1016/j.molcel.2014.01.017
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发表时间：
2014-03-06
期刊：
影响因子：
16
通讯作者：
Beggs, Jean D.
中科院分区：
文献类型：
--
作者：
Chathoth, Keerthi T.;Barrass, J. David;Webb, Shaun;Beggs, Jean D.
有充分的证据表明真核生物中剪接和转录之间的功能相互作用，但这些过程如何以及为何耦合仍然未知。 Prp5 蛋白 (Prp5p) 是酵母中前剪接体形成所需的 RNA 刺激的三磷酸腺苷酶 (ATPase)。我们通过体内 RNA 标记证明，除了剪接缺陷外，prp5-1 突变还会导致含内含子基因的转录缺陷。我们提供了转录延伸缺陷的染色质免疫沉淀证据，其中最大亚基七联体重复序列的 Ser5 处磷酸化的 RNA 聚合酶在内含子上积累，并且该缺陷需要 Cus2 蛋白。当 U2 snRNA 突变阻断前剪接体形成时，观察到类似的聚合酶积累。这些结果表明存在与共转录剪接体组装过程中前剪接体形成相关的转录延伸检查点。我们提出 Cus2p 作为转录中潜在检查点因子的作用。当前剪接体形成受阻时，转录延伸受到抑制 该缺陷的特征是 RNA 聚合酶在内含子上积累 该检查点可由 PRP5 或 U2 snRNA 的突变触发 U2 相关的 Cus2 蛋白是候选检查点因子 在真核生物中，转录和剪接在功能上相关，但如何或为何发生这种情况尚不清楚。查托斯等人。研究表明，在出芽酵母中，这些过程通过一个或多个与剪接机制监视相关的转录检查点耦合，因为剪接机制在新生转录物上进行共转录组装。
There is good evidence for functional interactions between splicing and transcription in eukaryotes, but how and why these processes are coupled remain unknown. Prp5 protein (Prp5p) is an RNA-stimulated adenosine triphosphatase (ATPase) required for prespliceosome formation in yeast. We demonstrate through in vivo RNA labeling that, in addition to a splicing defect, the prp5-1 mutation causes a defect in the transcription of intron-containing genes. We present chromatin immunoprecipitation evidence for a transcriptional elongation defect in which RNA polymerase that is phosphorylated at Ser5 of the largest subunit’s heptad repeat accumulates over introns and that this defect requires Cus2 protein. A similar accumulation of polymerase was observed when prespliceosome formation was blocked by a mutation in U2 snRNA. These results indicate the existence of a transcriptional elongation checkpoint that is associated with prespliceosome formation during cotranscriptional spliceosome assembly. We propose a role for Cus2p as a potential checkpoint factor in transcription. Transcriptional elongation is inhibited when prespliceosome formation is blocked The defect is characterized by RNA polymerase accumulation on introns This checkpoint can be triggered by mutations in either PRP5 or U2 snRNA The U2-associated Cus2 protein is a candidate checkpoint factor In eukaryotes, transcription and splicing are functionally linked, but how or why this happens is unknown. Chathoth et al. show that, in budding yeast, these processes are coupled by one or more transcriptional checkpoints associated with surveillance of the splicing machinery as it assembles cotranscriptionally on nascent transcripts.
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影响因子：
14.9
作者：
de Almeida SF;García-Sacristán A;Custódio N;Carmo-Fonseca M
通讯作者：
Carmo-Fonseca M
影响因子：
64.5
作者：
Ji X;Zhou Y;Pandit S;Huang J;Li H;Lin CY;Xiao R;Burge CB;Fu XD
通讯作者：
Fu XD
影响因子：
64.8
作者：
Hirose, Y;Manley, JL
通讯作者：
Manley, JL
影响因子：
16
作者：
Ahn, SH;Kim, M;Buratowski, S
通讯作者：
Buratowski, S
影响因子：
3.6
作者：
David, Charles J.;Manley, James L.
通讯作者：
Manley, James L.