The Ccr4-Not complex interacts with the mRNA export machinery.
The Ccr4-Not complex interacts with the mRNA export machinery.
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DOI：
10.1371/journal.pone.0018302
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发表时间：
2011-03-28
期刊：
影响因子：
3.7
通讯作者：
Laribee RN
中科院分区：
文献类型：
--
作者：
Kerr SC;Azzouz N;Fuchs SM;Collart MA;Strahl BD;Corbett AH;Laribee RN
Ccr4-Not复合物是真核生物基因转录和细胞质mRNA降解的关键调节因子。这种复合物是否也影响转录后基因调控的各个方面，如mRNA的输出，在很大程度上仍然没有探索。人Caf 1（hCaf 1）是Ccr4-Not复合体成员，与精氨酸甲基转移酶PRMT 1相互作用并调节该转移酶PRMT 1，其靶点包括参与mRNA输出的RNA结合蛋白。然而，人们对这一规定的功能意义知之甚少。在这里，我们证明使用免疫共沉淀方法，Ccr4-Not亚基与Hmt1，出芽酵母的PRMT1的直系同源物相互作用。此外，使用遗传和生物化学方法，我们证明，Ccr4-不物理和功能上与异源核核糖核蛋白（hnRNP）Nab2和Hrp1的相互作用，和物理协会取决于Hmt1甲基转移酶活性。利用质谱、免疫共沉淀和遗传学方法，我们还揭示了Ccr4-Not亚基与核孔复合物（NPC）组分之间的物理和功能相互作用，并提供了这些相互作用影响mRNA输出的证据。综上所述，我们的研究结果表明，Ccr4-Not与mRNA加工/输出途径有着以前未实现的功能联系，这可能对其在基因表达中的作用很重要。这些结果进一步揭示了Ccr4-Not的生物学功能，并表明该复合物参与了mRNA生物合成的各个方面，从转录调节到mRNA输出和周转。
The Ccr4-Not complex is a key eukaryotic regulator of gene transcription and cytoplasmic mRNA degradation. Whether this complex also affects aspects of post-transcriptional gene regulation, such as mRNA export, remains largely unexplored. Human Caf1 (hCaf1), a Ccr4-Not complex member, interacts with and regulates the arginine methyltransferase PRMT1, whose targets include RNA binding proteins involved in mRNA export. However, the functional significance of this regulation is poorly understood. Here we demonstrate using co-immunoprecipitation approaches that Ccr4-Not subunits interact with Hmt1, the budding yeast ortholog of PRMT1. Furthermore, using genetic and biochemical approaches, we demonstrate that Ccr4-Not physically and functionally interacts with the heterogenous nuclear ribonucleoproteins (hnRNPs) Nab2 and Hrp1, and that the physical association depends on Hmt1 methyltransferase activity. Using mass spectrometry, co-immunoprecipitation and genetic approaches, we also uncover physical and functional interactions between Ccr4-Not subunits and components of the nuclear pore complex (NPC) and we provide evidence that these interactions impact mRNA export. Taken together, our findings suggest that Ccr4-Not has previously unrealized functional connections to the mRNA processing/export pathway that are likely important for its role in gene expression. These results shed further insight into the biological functions of Ccr4-Not and suggest that this complex is involved in all aspects of mRNA biogenesis, from the regulation of transcription to mRNA export and turnover.
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