一種與內質網相關的促進3‘UTR介導的蛋白互做的無膜細胞器_2018_cell_Weirui Ma, Christine Mayr

A Membraneless Organelle Associated with the Endoplasmic Reticulum Enables 3′UTR-Mediated Protein-Protein Interactions

一種與內質網相關的促進3‘UTR介導的蛋白互做的無膜細胞器

 

Cell　Volume 175, Issue 6, 29 November 2018, Pages 1492-1506.e19

First author: Weirui Ma

Corresponding: Christine Mayr

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

 

Abbrs

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 顆粒是纏繞在內質網上的無膜細胞器

 •　　TIS11B 在胞內造成 TIS 顆粒，富集或排斥特異 mRNA

 •　　TIS 顆粒使 AU-rich 的 mRNA 可以在內質網亞域翻譯

 •　　特異的蛋白互做只可以在 TIS 顆粒區域造成

 

Results

TIS11B 造成纏繞於內質網的網狀 assemblies

TIS11B Forms Reticular Assemblies that Are Intertwined with the ER

 

3‘UTR 區含有大量 AREs 的編碼膜蛋白的 mRNAs 被富集在 TIS 顆粒

Membrane Protein-Encoding mRNAs that Contain Multiple AREs in Their 3′UTRs Are Enriched in TIS Granules

 

TIS 顆粒富集特異蛋白

TIS Granules Enrich Specific Proteins

 

TIS11B 對 3’UTR 依賴的 SET 和 CD47-LU 互做，以及隨後的 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 過表達，SET 無過表達，增長 3‘UTR 介導的 CD47-LU 表面定位

Overexpression of TIS11B, but Not Overexpression of SET, Increases 3′UTR-Mediated Surface Localization of CD47-LU

 

TIS 顆粒對於 SET 和膜蛋白的蛋白互做是必需且足夠的

TIS Granules Are Necessary and Sufficient for the Protein-Protein Interaction between SET and Membrane Proteins

 

電荷分佈驅動的 TIS11B 裝配是 3'UTR 介導的蛋白互做須要的

TIS11B Assembly Is Charge Pattern-Driven and Is Required for 3′UTR-Mediated Protein-Protein Interactions

 

TIS11B 是 TIS 顆粒的 scaffold

TIS11B Is the Scaffold of TIS Granules

 

TIS11B 表達普遍，TIS 顆粒構成在脊椎動物中保守

TIS11B Is Widely Expressed and TIS Granule Formation Is Conserved among Vertebrates

 

TIS 顆粒的區域與胞質具備不一樣的生物物理和生化屬性

The TIS Granule Region Has Different Biophysical and Biochemical Properties Than the Cytoplasm

 

Discussion

TIS 顆粒在生理條件下造成，並造成一個網狀組織纏繞於內質網

TIS Granules Form under Physiological Conditions and Create a Meshwork Intertwined with the ER

 

TIS 顆粒可以使 3’UTR 編碼的遺傳信息轉遞至蛋白

TIS Granules Enable Transmission of 3′UTR-Encoded Genetic Information to Proteins

 

特異的蛋白互做是創建在不能在此亞細胞區室外造成的 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 在這個過程當中扮演數個角色

3′UTRs Play Several Roles in This Process

 

TIS11B 表達普遍，TIS 顆粒構成在脊椎動物中保守

TIS11B Is Widely Expressed and TIS Granule Formation Is Conserved among Vertebrates

 

TIS 顆粒區域的生化和生物物理環境怎樣促進特異的蛋白互做仍然很是不清楚

It Is Still Largely Unclear How the Biochemical and Biophysical Environment of the TIS Granule Region Promotes Specific Protein-Protein Interactions