A Membraneless Organelle Associated with the Endoplasmic Reticulum Enables 3′UTR-Mediated Protein-Protein Interactions
一种与内质网相关的促进3‘UTR介导的蛋白互作的无膜细胞器
Cell Volume 175, Issue 6, 29 November 2018, Pages 1492-1506.e19
一作 Weirui Ma
通讯 Christine Mayr
单位 Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
https://doi.org/10.1016/j.cell.2018.10.007
Some Proper Nouns
ARE : AU-rich element
CD47 : CD47 (Cluster of Differentiation 47) also known as integrin associated protein (IAP) is a transmembrane protein
CD47-LU : CD47-Long 3'UTR isoform
CD47-SU : CD47-Short 3'UTR isoform
SET : Multitasking protein, involved in apoptosis, transcription, nucleosome assembly and histone chaperoning.
TIS11B : Protein is encoded by the ZFP36L1 gene, which is widely expressed across human tissues and cell types
TIGER : TIS granule-ER
HuR : An RNA-binding protein
HSPA8 : Heat shock 70 kDa protein 8 also known as heat shock cognate 71 kDa protein or Hsc70 or Hsp73 is a heat shock protein that in humans is encoded by the HSPA8 gene on chromosome 11.
PD-L1 : Programmed death-ligand 1 (PD-L1) also known as cluster of differentiation 274 (CD274) or B7 homolog 1 (B7-H1) is a protein that in humans is encoded by the CD274 gene.
mCherry : a member of the mFruits family of monomeric red fluorescent proteins (mRFPs)
Highlights
• TIS 颗粒是缠绕在内质网上的无膜细胞器
• TIS11B 在胞内形成 TIS 颗粒，富集或排斥特异 mRNA
• TIS 颗粒使 AU-rich 的 mRNA 能够在内质网亚域翻译 (AU-rich element = ARE)
• 特异的蛋白互作只能够在 TIS 颗粒区域形成
Summary
Introduction
Results
TIS11B 形成缠绕于内质网的网状 assemblies
TIS11B Forms Reticular Assemblies that Are Intertwined with the ER
3‘UTR 区含有大量 AREs 的编码膜蛋白的 mRNAs 被富集在 TIS 颗粒
Membrane Protein-Encoding mRNAs that Contain Multiple AREs in Their 3′UTRs Are Enriched in TIS Granules
TIS 颗粒富集特异蛋白
TIS Granules Enrich Specific Proteins
TIS11B 对 3’UTR 依赖的 SET 和 CD47-LU 互作，以及随后的 CD47-LU 在表面定位是必需的
TIS11B Is Necessary for 3′UTR-Dependent Interaction between SET and CD47-LU and for Subsequent Surface Localization of CD47-LU
TIS11B 过表达，SET 无过表达，增加 3‘UTR 介导的 CD47-LU 表面定位
Overexpression of TIS11B, but Not Overexpression of SET, Increases 3′UTR-Mediated Surface Localization of CD47-LU
TIS 颗粒对于 SET 和膜蛋白的蛋白互作是必需且足够的
TIS Granules Are Necessary and Sufficient for the Protein-Protein Interaction between SET and Membrane Proteins
电荷分布驱动的 TIS11B 装配是 3'UTR 介导的蛋白互作需要的
TIS11B Assembly Is Charge Pattern-Driven and Is Required for 3′UTR-Mediated Protein-Protein Interactions
TIS11B 是 TIS 颗粒的 scaffold
TIS11B Is the Scaffold of TIS Granules
TIS11B 表达广泛，TIS 颗粒构成在脊椎动物中保守
TIS11B Is Widely Expressed and TIS Granule Formation Is Conserved among Vertebrates
TIS 颗粒的区域与胞质具有不同的生物物理和生化属性
The TIS Granule Region Has Different Biophysical and Biochemical Properties Than the Cytoplasm
Discussion
TIS 颗粒在生理条件下形成，并形成一个网状组织缠绕于内质网
TIS Granules Form under Physiological Conditions and Create a Meshwork Intertwined with the ER
TIS 颗粒能够使 3’UTR 编码的遗传信息转递至蛋白
TIS Granules Enable Transmission of 3′UTR-Encoded Genetic Information to Proteins
特异的蛋白互作是建立在不能在此亚细胞区室外形成的 TIGER 域上的 (TIGER = TIS granule-ER)
Specific Protein-Protein Interactions Are Established in the TIGER Domain that Cannot Form outside of This Compartment
3‘UTR 在这个过程中扮演数个角色
3′UTRs Play Several Roles in This Process
TIS11B 表达广泛，TIS 颗粒构成在脊椎动物中保守
TIS11B Is Widely Expressed and TIS Granule Formation Is Conserved among Vertebrates
TIS 颗粒区域的生化和生物物理环境怎样促进特异的蛋白互作仍然非常不清楚
It Is Still Largely Unclear How the Biochemical and Biophysical Environment of the TIS Granule Region Promotes Specific Protein-Protein Interactions
