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

Autor: Robert J. Lee, Frances A. Collins, George S. Vassiliou, Yi Zheng, Andreas Petri, Krzysztof Mrózek, Sara Terreri, Prasanthi Kumchala, Christopher J. Walker, Deedra Nicolet, Kellie J. Archer, Michael A. Freitas, Nina C. Zitzer, Felice Pepe, Guramrit Singh, Eric Wang, Allison E. Walker, Virginia Camilotto, Sakari Kauppinen, Adrienne M. Dorrance, Lauren A. Woodward, Miranda L. Gardner, Jonathan L. Cooper, Ramiro Garzon, Jessica Kohlschmidt, Dimitrios Papaioannou, Xiongwei Cai, Xiaoqing Rong-Mullins, Iannis Aifantis, Clara D. Bloomfield, Marius Bill, Oliver M. Dovey, Malith Karunasiri
Přispěvatelé: Petri, Andreas [0000-0002-0425-5794], Pepe, Felice [0000-0001-6507-9993], Rong-Mullins, Xiaoqing [0000-0002-2122-552X], Archer, Kellie J [0000-0003-1555-5781], Vassiliou, George [0000-0003-4337-8022], Singh, Guramrit [0000-0002-5283-9540], Bloomfield, Clara D [0000-0001-5465-7591], Apollo - University of Cambridge Repository, Archer, Kellie J. [0000-0003-1555-5781], Bloomfield, Clara D. [0000-0001-5465-7591]
Rok vydání: 2019
Předmět:
0301 basic medicine
Transcription
Genetic
Molecular biology
THP-1 Cells
45/88
General Physics and Astronomy
Mice
SCID
Non-coding RNAs
0302 clinical medicine
42/89
Transcription (biology)
Mice
Inbred NOD
hemic and lymphatic diseases
631/337/572
38/22
Protein biosynthesis
lcsh:Science
Cancer
Mice
Knockout
Multidisciplinary
Molecular medicine
article
Myeloid leukemia
Nuclear Proteins
Long non-coding RNA
3. Good health
Cell biology
Leukemia
Leukemia
Myeloid
030220 oncology & carcinogenesis
Acute Disease
RNA
Long Noncoding
Transcription
Nucleophosmin
631/337
631/67
NPM1
Science
Transplantation
Heterologous
38/90
Biology
General Biochemistry
Genetics and Molecular Biology
38/91
14/1
03 medical and health sciences
Cell Line
Tumor
38/89
medicine
Animals
Humans
38/109
Cell Proliferation
45/91
RNA
General Chemistry
Ribosomal RNA
45/15
medicine.disease
692/4017
030104 developmental biology
HEK293 Cells
RNA
Ribosomal
Protein Biosynthesis
Mutation
631/337/384
lcsh:Q
K562 Cells
Zdroj: Nature Communications, Vol 10, Iss 1, Pp 1-15 (2019)
Papaioannou, D, Petri, A, Dovey, O M, Terreri, S, Wang, E, Collins, F A, Woodward, L A, Walker, A E, Nicolet, D, Pepe, F, Kumchala, P, Bill, M, Walker, C J, Karunasiri, M, Mrózek, K, Gardner, M L, Camilotto, V, Zitzer, N, Cooper, J L, Cai, X, Rong-Mullins, X, Kohlschmidt, J, Archer, K J, Freitas, M A, Zheng, Y, Lee, R J, Aifantis, I, Vassiliou, G, Singh, G, Kauppinen, S, Bloomfield, C D, Dorrance, A M & Garzon, R 2019, ' The long non-coding RNA HOXB-AS3 regulates ribosomal RNA transcription in NPM1-mutated acute myeloid leukemia ', Nature Communications, vol. 10, no. 1, 5351 . https://doi.org/10.1038/s41467-019-13259-2
Nature Communications
DOI: 10.1038/s41467-019-13259-2
Popis: 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.
LncRNAs at the HOX gene locus are increased in expression in NPM1 mutant acute myeloid leukemia. In this study, the authors show that one such lncRNA, HOX3B-AS3, has a role in regulating gene transcription and protein synthesis in leukemia cells.
Databáze: OpenAIRE
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