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体内重建发现多价 RNA-RNA 相互作用是网格状凝聚物的驱动力。

In vivo reconstitution finds multivalent RNA-RNA interactions as drivers of mesh-like condensates.

机构信息

Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, United States.

Structural Biology Program, Memorial Sloan Kettering Cancer Center, New York, United States.

出版信息

Elife. 2021 Mar 2;10:e64252. doi: 10.7554/eLife.64252.

Abstract

Liquid-like condensates have been thought to be sphere-like. Recently, various condensates with filamentous morphology have been observed in cells. One such condensate is the TIS granule network that shares a large surface area with the rough endoplasmic reticulum and is important for membrane protein trafficking. It has been unclear how condensates with mesh-like shapes but dynamic protein components are formed. In vitro and in vivo reconstitution experiments revealed that the minimal components are a multivalent RNA-binding protein that concentrates RNAs that are able to form extensive intermolecular mRNA-mRNA interactions. mRNAs with large unstructured regions have a high propensity to form a pervasive intermolecular interaction network that acts as condensate skeleton. The underlying RNA matrix prevents full fusion of spherical liquid-like condensates, thus driving the formation of irregularly shaped membraneless organelles. The resulting large surface area may promote interactions at the condensate surface and at the interface with other organelles.

摘要

液滴状凝聚物曾被认为是球状的。最近,在细胞中观察到了各种具有丝状形态的凝聚物。其中一种凝聚物是 TIS 颗粒网络,它与粗糙内质网具有很大的表面积,对于膜蛋白运输很重要。目前尚不清楚如何形成具有网状形状但具有动态蛋白质成分的凝聚物。体外和体内重建实验表明,最小的成分是一种多价 RNA 结合蛋白,它浓缩能够形成广泛的分子间 mRNA-mRNA 相互作用的 RNA。具有大的无结构区域的 mRNAs 具有形成普遍的分子间相互作用网络的高倾向,该网络充当凝聚物的骨架。基础 RNA 基质防止球形液滴状凝聚物完全融合,从而驱动无膜细胞器的形成。由此产生的大表面积可能促进凝聚物表面的相互作用以及与其他细胞器的界面相互作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8c2/7968931/984a70cb588e/elife-64252-fig1.jpg

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