lncRNA requirements for mouse acute myeloid leukemia and normal differentiation.

Abstract

A substantial fraction of the genome is transcribed in a cell-type-specific manner, producing long non-coding RNAs (lncRNAs), rather than protein-coding transcripts. Here, we systematically characterize transcriptional dynamics during hematopoiesis and in hematological malignancies. Our analysis of annotated and de novo assembled lncRNAs showed many are regulated during differentiation and mis-regulated in disease. We assessed lncRNA function via an in vivo RNAi screen in a model of acute myeloid leukemia. This identified several lncRNAs essential for leukemia maintenance, and found that a number act by promoting leukemia stem cell signatures. Leukemia blasts show a myeloid differentiation phenotype when these lncRNAs were depleted, and our data indicates that this effect is mediated via effects on the MYC oncogene. Bone marrow reconstitutions showed that a lncRNA expressed across all progenitors was required for the myeloid lineage, whereas the other leukemia-induced lncRNAs were dispensable in the normal setting.

• Authors: M Joaquina Delás, Leah R Sabin, Egor Dolzhenko, Simon Rv Knott, Ester Munera Maravilla, Benjamin T Jackson, Sophia A Wild, Tatjana Kovacevic, Eva Maria Stork, Meng Zhou, Nicolas Erard, Emily Lee, David R Kelley, Mareike Roth, Inês Am Barbosa, Johannes Zuber, John L Rinn, Andrew D Smith, Gregory J Hannon
• Journal: eLife (Elife) Vol. 6 (09 06 2017) ISSN: 2050-084X [Electronic] England
• PMID: 28875933 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• RNA, Long Noncoding

Topics

• Animals
• Cell Differentiation
• Disease Models, Animal
• Gene Expression Profiling
• Gene Expression Regulation
• Hematopoiesis
• Leukemia, Myeloid, Acute (pathology)
• Mice
• RNA, Long Noncoding (genetics, metabolism)