PDF(Pubmed)
Abstract：
The nucleolus is a subnuclear compartment critical in ribosome biogenesis and cellular stress responses. These mechanisms are governed by a complex interplay of proteins, including NOC1, a member of the NOC family of nucleolar proteins responsible for controlling rRNA processing and ribosomal maturation. This study reveals a novel relationship between NOC1 and MYC transcription factor, known for its crucial role in controlling ribosomal biogenesis, cell growth, and proliferation. Here, we demonstrate that NOC1 functions as a direct target of MYC, as it is transcriptionally induced through a functional MYC-binding E-box sequence in the NOC1 promoter region. Furthermore, protein interactome analysis reveals that NOC1-complex includes the nucleolar proteins NOC2 and NOC3 and other nucleolar components such as Nucleostemin1 Ns1 transporters of ribosomal subunits and components involved in rRNA processing and maturation. In response to MYC, NOC1 expression and localization within the nucleolus significantly increase, suggesting a direct functional link between MYC activity and NOC1 function. Notably, NOC1 over-expression leads to the formation of large nuclear granules and enlarged nucleoli, which co-localize with nucleolar fibrillarin and Ns1. Additionally, we demonstrate that NOC1 expression is necessary for Ns1 nucleolar localization, suggesting a role for NOC1 in maintaining nucleolar structure. Finally, the co-expression of NOC1 and MYC enhances nucleolus size and maintains their co-localization, outlining another aspect of the cooperation between NOC1 and MYC in nucleolar dynamics. This study also reveals an enrichment with NOC1 with few proteins involved in RNA processing, modification, and splicing. Moreover, proteins such as Ythdc1, Flacc, and splenito are known to mediate N6-methyladenosine (m6A) methylation of mRNAs in nuclear export, revealing NOC1\'s potential involvement in coordinating RNA splicing and nuclear mRNA export. In summary, we uncovered novel roles for NOC1 in nucleolar homeostasis and established its direct connection with MYC in the network governing nucleolar structure and function. These findings also highlight NOC1\'s interaction with proteins relevant to specific RNA functions, suggesting a broader role in addition to its control of nucleolar homeostasis and providing new insight that can be further investigated.
摘要：
核仁是核糖体生物发生和细胞应激反应中至关重要的亚核隔室。这些机制由蛋白质的复杂相互作用控制，包括NOC1,其是负责控制rRNA加工和核糖体成熟的核仁蛋白NOC家族的成员。这项研究揭示了NOC1和MYC转录因子之间的新关系，以其在控制核糖体生物发生中的关键作用而闻名，细胞生长,和扩散。这里,我们证明NOC1是MYC的直接靶标，因为它是通过NOC1启动子区域中的功能性MYC结合E-box序列转录诱导的。此外，蛋白质相互作用组分析显示，NOC1复合物包括核仁蛋白NOC2和NOC3以及其他核仁成分，例如核糖体亚基的核茎素1Ns1转运蛋白以及参与rRNA加工和成熟的成分。为了回应MYC，NOC1在核仁内的表达和定位显著增加，表明MYC活性和NOC1功能之间存在直接的功能联系。值得注意的是,NOC1过度表达导致形成大的核颗粒和扩大的核仁,与核仁原纤和Ns1共定位。此外,我们证明NOC1表达对于Ns1核仁定位是必需的，提示NOC1在维持核仁结构中的作用。最后,NOC1和MYC的共表达增强了核仁大小并保持了它们的共定位，概述了NOC1和MYC在核仁动力学中合作的另一个方面。这项研究还揭示了NOC1的富集，很少有蛋白质参与RNA加工，修改,和拼接。此外，蛋白质，如Ythdc1，Flacc，和脾已知介导N6-甲基腺苷（m6A）甲基化的mRNA在核输出，揭示NOC1可能参与协调RNA剪接和核mRNA输出。总之,我们发现了NOC1在核仁稳态中的新作用，并在控制核仁结构和功能的网络中建立了与MYC的直接联系。这些发现还强调了NOC1与特定RNA功能相关蛋白质的相互作用，除了控制核仁稳态外，它还具有更广泛的作用，并提供了可以进一步研究的新见解。
