The asymmetrically segregating IncRNA cherub is required for transforming stem cells into malignant cells

被引:27
作者
Landskron, Lisa [1 ]
Steinmann, Victoria [1 ]
Bonney, Francois [1 ]
Burkard, Thomas R. [1 ]
Steinmann, Jonas [1 ]
Reichardt, Ilka [1 ]
Harzer, Heike [1 ]
Laurenson, Anne-Sophie [2 ]
Reichert, Heinrich [2 ]
Knoblich, Juergen A. [1 ]
机构
[1] Austrian Acad Sci, Inst Mol Biotechnol, IMBA, Vienna, Austria
[2] Univ Basel, Biozentrum, Basel, Switzerland
来源
ELIFE | 2018年 / 7卷
基金
奥地利科学基金会;
关键词
NEUROBLAST SELF-RENEWAL; GENOME-WIDE ANALYSIS; NEURAL STEM; TUMOR-SUPPRESSOR; MESSENGER-RNA; BRAIN-TUMOR; DROSOPHILA-MELANOGASTER; GENE AMPLIFICATION; FACS PURIFICATION; ORTHOLOG TRIM3;
D O I
10.7554/eLife.31347
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Tumor cells display features that are not found in healthy cells. How they become immortal and how their specific features can be exploited to combat tumorigenesis are key questions in tumor biology. Here we describe the long non-coding RNA cherub that is critically required for the development of brain tumors in Drosophila but is dispensable for normal development. In mitotic Drosophila neural stem cells, cherub localizes to the cell periphery and segregates into the differentiating daughter cell. During tumorigenesis, de-differentiation of cherub-high cells leads to the formation of tumorigenic stem cells that accumulate abnormally high cherub levels. We show that cherub establishes a molecular link between the RNA-binding proteins Staufen and Syncrip. As Syncrip is part of the molecular machinery specifying temporal identity in neural stem cells, we propose that tumor cells proliferate indefinitely, because cherub accumulation no longer allows them to complete their temporal neurogenesis program.
引用
收藏
页数:35
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