The long non-coding RNA HOXB-AS3 regulates ribosomal RNA transcription in NPM1-mutated acute myeloid leukemia

Dimitrios Papaioannou, Andreas Petri, Oliver M Dovey, Sara Terreri, Eric Wang, Frances A Collins, Lauren A Woodward, Allison E Walker, Deedra Nicolet, Felice Pepe, Prasanthi Kumchala, Marius Bill, Christopher J Walker, Malith Karunasiri, Krzysztof Mrózek, Miranda L Gardner, Virginia Camilotto, Nina Zitzer, Jonathan L Cooper, Xiongwei CaiXiaoqing Rong-Mullins, Jessica Kohlschmidt, Kellie J Archer, Michael A Freitas, Yi Zheng, Robert J Lee, Iannis Aifantis, George Vassiliou, Guramrit Singh, Sakari Kauppinen, Clara D Bloomfield, Adrienne M Dorrance, Ramiro Garzon

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Abstract

Long non-coding RNAs (lncRNAs) are important regulatory molecules that are implicated in cellular physiology and pathology. In this work, we dissect the functional role of the HOXB-AS3 lncRNA in patients with NPM1-mutated (NPM1mut) acute myeloid leukemia (AML). We show that HOXB-AS3 regulates the proliferative capacity of NPM1mut AML blasts in vitro and in vivo. HOXB-AS3 is shown to interact with the ErbB3-binding protein 1 (EBP1) and guide EBP1 to the ribosomal DNA locus. Via this mechanism, HOXB-AS3 regulates ribosomal RNA transcription and de novo protein synthesis. We propose that in the context of NPM1 mutations, HOXB-AS3 overexpression acts as a compensatory mechanism, which allows adequate protein production in leukemic blasts.

OriginalsprogEngelsk
Artikelnummer5351
TidsskriftNature Communications
Vol/bind10
Udgave nummer1
Antal sider15
ISSN2041-1723
DOI
StatusUdgivet - 25 nov. 2019

Bibliografisk note

Publisher Correction:
"The original version of this Article contained an error in the author affiliations.
Affiliation number 9 incorrectly read “Department of Molecular Medicine, University of Pavia, Pavia, USA”
This has now been corrected in both the PDF and HTML versions of the Article."
(Nat Commun 11, 204 (2020). https://doi.org/10.1038/s41467-019-13969-7).

Author Correction:
"The original version of this article omitted the following from the Acknowledgements: R.G. was supported by a Scholar in Clinical Research award from The Leukemia & Lymphoma Society."
This has now been corrected in both the PDF and HTML versions of the article.
(Nat Commun 11:3878 (2020). https://doi.org/10.1038/s41467-020-17746-9.

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