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

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 researchers from the IMBA Vienna 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. The researchers 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.

 The lncRNA CR43283 is upregulated in brat tumor neuroblasts

lncRNA

(A) Cartoon illustrating the strategy to isolate NBII and tNBs. (B) Schematic overview of DigiTAG. cDNA fragments of the sequencing library harbor random 8-mer index tags (barcodes) unique for each individual molecule. After sequencing, reads are mapped and barcodes are assigned to each read. Reads with identical barcodes are removed to avoid amplification biases.

Landskron L, Steinmann V, Bonnay F, Burkard TR, Steinmann J, Reichardt I, Harzer H, Laurenson AS, Reichert H, Knoblich JA. (2018) The asymmetrically segregating lncRNA cherub is required for transforming stem cells into malignant cells. Elife 7: e31347. [article]

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