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lncRNAs maintain the functional phase state of nucleolar prion-like protein to facilitate rRNA processing
Molecular Cell ( IF 14.5 ) Pub Date : 2024-11-22 , DOI: 10.1016/j.molcel.2024.10.036
Yu-Meng Sun, Shun-Xin Zhu, Xiao-Tong Chen, Qi Pan, Yan An, Tian-Qi Chen, Heng-Jing Huang, Ke-Jia Pu, Jun-Yi Lian, Wen-Long Zhao, Wen-Tao Wang, Yue-Qin Chen

Liquid-to-solid phase transition of proteins with prion-like domains (PLDs) has been associated with neurodegenerative diseases and aging. High protein concentration is one important aspect triggering the transition; however, several prion-like proteins, including fibrillarin (FBL), an important phase-separated protein in the nucleolus for pre-rRNA processing, show relatively high expression levels in certain cells, especially cancer cells, without obvious phase transitions and growth arrest. How cells maintain prion-like protein proteostasis is still unknown. Here, we attempt to answer the question, with FBL as an example. We find that lncRNA DNAJC3-AS1 can buffer the behavior of FBL condensation and maintain the state and function of fibrillar component/dense fibrillar component (FC/DFC) units in human cell lines through two mechanisms, not only facilitating FBL condensation but also inhibiting excessive aggregation by binding multiple PLDs and partially blocking their interactions. We propose that lncRNAs could supply buffered systems to sustain functional phase states of prion-like proteins.

中文翻译:


lncRNA 维持核仁朊病毒样蛋白的功能相态,以促进 rRNA 加工



具有朊病毒样结构域 (PLD) 的蛋白质的液-固相变与神经退行性疾病和衰老有关。高蛋白质浓度是触发转变的一个重要方面;然而,几种朊病毒样蛋白,包括纤维蛋白 (FBL),一种在核仁中用于 pre-rRNA 加工的重要相分离蛋白,在某些细胞(尤其是癌细胞)中显示出相对较高的表达水平,没有明显的相变和生长停滞。细胞如何维持朊病毒样蛋白质的蛋白质稳态仍然未知。在这里,我们尝试以 FBL 为例来回答这个问题。我们发现 lncRNA DNAJC3-AS1 可以通过两种机制缓冲人细胞系中 FBL 缩合的行为并维持纤维组分/致密纤维组分 (FC/DFC) 单元的状态和功能,不仅可以促进 FBL 缩合,还可以通过结合多个 PLD 并部分阻断它们的相互作用来抑制过度聚集。我们提出 lncRNAs 可以提供缓冲系统来维持朊病毒样蛋白的功能相态。
更新日期:2024-11-22
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