Rpb4 and Puf3 imprint and post-transcriptionally control the stability of a common set of mRNAs in yeast
Rpb4 and Puf3 imprint and post-transcriptionally control the stability of a common set of mRNAs in yeast
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DOI：
10.1080/15476286.2020.1839229
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发表时间：
2020-11-02
期刊：
影响因子：
4.1
通讯作者：
Navarro, F.
中科院分区：
文献类型：
--
作者：
Garrido-Godino, A. I.;Gupta, I.;Navarro, F.
涉及RNA聚合酶II的基因表达受mRNA合成和降解之间的协同相互作用调节，其中mRNA衰变机制和转录机制分别影响转录和mRNA稳定性。Rpb 4和可能的二聚体Rpb 4/7似乎是控制这些过程的RNA pol II的中心组分。在这项工作中，我们解开了Rpb 4参与的介导转录后事件调节mRNA印记和稳定性的分子机制。通过RIP-Seq，我们在全基因组范围内分析了Rpb 4与mRNA的关联，并证明它靶向了超过1400个转录本的大群体。这些mRNA中的一组也是RNA结合蛋白Puf 3的靶点。我们证明了Rpb 4和Puf 3在物理上，遗传上和功能上相互作用，也影响mRNA的稳定性，并可能影响一组共同的mRNA的印记。此外，Rpb 4和Puf 3与mRNA的结合相互依赖。我们还首次证明了Puf 3以Rpb 4依赖的方式与染色质结合。我们的数据还表明，Rpb 4可能是RNA pol II的关键元件，与RBP合作协调mRNA合成，印迹和稳定性。
Gene expression involving RNA polymerase II is regulated by the concerted interplay between mRNA synthesis and degradation, crosstalk in which mRNA decay machinery and transcription machinery respectively impact transcription and mRNA stability. Rpb4, and likely dimer Rpb4/7, seem the central components of the RNA pol II governing these processes. In this work we unravel the molecular mechanisms participated by Rpb4 that mediate the posttranscriptional events regulating mRNA imprinting and stability. By RIP-Seq, we analysed genome-wide the association of Rpb4 with mRNAs and demonstrated that it targeted a large population of more than 1400 transcripts. A group of these mRNAs was also the target of the RNA binding protein, Puf3. We demonstrated that Rpb4 and Puf3 physically, genetically, and functionally interact and also affect mRNA stability, and likely the imprinting, of a common group of mRNAs. Furthermore, the Rpb4 and Puf3 association with mRNAs depends on one another. We also demonstrated, for the first time, that Puf3 associates with chromatin in an Rpb4-dependent manner. Our data also suggest that Rpb4 could be a key element of the RNA pol II that coordinates mRNA synthesis, imprinting and stability in cooperation with RBPs.