当前位置: X-MOL 学术Science › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
MRNA structure determines specificity of a polyQ-driven phase separation
Science ( IF 56.9 ) Pub Date : 2018-04-12 , DOI: 10.1126/science.aar7432
Erin M. Langdon 1 , Yupeng Qiu 2 , Amirhossein Ghanbari Niaki 2 , Grace A. McLaughlin 1 , Chase A. Weidmann 3 , Therese M. Gerbich 1 , Jean A. Smith 1 , John M. Crutchley 1 , Christina M. Termini 4 , Kevin M. Weeks 3 , Sua Myong 2 , Amy S. Gladfelter 1, 5
Affiliation  

RNA and membraneless organelles Membraneless compartments can form in cells through liquidliquid phase separation (see the Perspective by Polymenidou). But what prevents these cellular condensates from randomly fusing together? Using the RNA-binding protein (RBP) Whi3, Langdon et al. demonstrated that the secondary structure of different RNA components determines the distinct biophysical and biological properties of the two types of condensates that Whi3 forms. Several RBPs, such as FUS and TDP43, contain prion-like domains and are linked to neurodegenerative diseases. These RBPs are usually soluble in the nucleus but can form pathological aggregates in the cytoplasm. Maharana et al. showed that local RNA concentrations determine distinct phase separation behaviors in different subcellular locations. The higher RNA concentrations in the nucleus act as a buffer to prevent phase separation of RBPs; when mislocalized to the cytoplasm, lower RNA concentrations trigger aggregation. Science, this issue p. 922, p. 918; see also p. 859 Certain RNA sequences, via secondary structures, specify the molecular properties of phase-separated cellular condensates. RNA promotes liquid-liquid phase separation (LLPS) to build membraneless compartments in cells. How distinct molecular compositions are established and maintained in these liquid compartments is unknown. Here, we report that secondary structure allows messenger RNAs (mRNAs) to self-associate and determines whether an mRNA is recruited to or excluded from liquid compartments. The polyQ-protein Whi3 induces conformational changes in RNA structure and generates distinct molecular fluctuations depending on the RNA sequence. These data support a model in which structure-based, RNA-RNA interactions promote assembly of distinct droplets and protein-driven, conformational dynamics of the RNA maintain this identity. Thus, the shape of RNA can promote the formation and coexistence of the diverse array of RNA-rich liquid compartments found in a single cell.

中文翻译:

mRNA 结构决定了 polyQ 驱动相分离的特异性

RNA 和无膜细胞器 无膜区室可以通过液液相分离在细胞中形成(参见 Polymenidou 的观点)。但是是什么阻止了这些细胞凝聚物随机融合在一起呢?使用 RNA 结合蛋白 (RBP) Whi3,Langdon 等人。证明不同 RNA 组分的二级结构决定了 Whi3 形成的两种类型的缩合物的不同生物物理和生物学特性。几种 RBP,例如 FUS 和 TDP43,包含类似朊病毒的结构域,并且与神经退行性疾病有关。这些 RBP 通常可溶于细胞核,但可在细胞质中形成病理性聚集体。马哈拉纳等人。表明局部 RNA 浓度决定了不同亚细胞位置的不同相分离行为。细胞核中较高的 RNA 浓度充当缓冲液,以防止 RBP 的相分离;当错误定位到细胞质时,较低的 RNA 浓度会引发聚集。科学,这个问题 p。922,第。918; 另见第。859 某些 RNA 序列通过二级结构指定相分离细胞凝聚物的分子特性。RNA 促进液-液相分离 (LLPS) 以在细胞中构建无膜隔室。在这些液体隔室中如何建立和维持不同的分子组成是未知的。在这里,我们报告二级结构允许信使 RNA (mRNA) 自我关联并确定 mRNA 是被招募到液体隔间还是从液体隔间中排除。polyQ 蛋白 Whi3 诱导 RNA 结构的构象变化,并根据 RNA 序列产生不同的分子波动。这些数据支持一个模型,其中基于结构的 RNA-RNA 相互作用促进不同液滴的组装,而蛋白质驱动的 RNA 构象动力学保持这种特性。因此,RNA 的形状可以促进在单个细胞中发现的各种富含 RNA 的液体区室的形成和共存。
更新日期:2018-04-12
down
wechat
bug