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

Author

Listed:
  • Dimitrios Papaioannou

    (The Ohio State University, Comprehensive Cancer Center)

  • Andreas Petri

    (Aalborg University)

  • Oliver M. Dovey

    (Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus)

  • Sara Terreri

    (Institute of Genetics and Biophysics (IGB-ABT), National Council of Research (CNR))

  • Eric Wang

    (New York University School of Medicine)

  • Frances A. Collins

    (The Ohio State University, Comprehensive Cancer Center)

  • Lauren A. Woodward

    (The Ohio State University)

  • Allison E. Walker

    (The Ohio State University, Comprehensive Cancer Center)

  • Deedra Nicolet

    (The Ohio State University, Comprehensive Cancer Center
    The Ohio State University)

  • Felice Pepe

    (The Ohio State University, Comprehensive Cancer Center)

  • Prasanthi Kumchala

    (The Ohio State University, Comprehensive Cancer Center)

  • Marius Bill

    (The Ohio State University, Comprehensive Cancer Center)

  • Christopher J. Walker

    (The Ohio State University, Comprehensive Cancer Center)

  • Malith Karunasiri

    (The Ohio State University, Comprehensive Cancer Center)

  • Krzysztof Mrózek

    (The Ohio State University, Comprehensive Cancer Center)

  • Miranda L. Gardner

    (The Ohio State University, Comprehensive Cancer Center
    The Ohio State University)

  • Virginia Camilotto

    (Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus
    University of Pavia)

  • Nina Zitzer

    (The Ohio State University, Comprehensive Cancer Center)

  • Jonathan L. Cooper

    (Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus)

  • Xiongwei Cai

    (Cincinnati Children’s Hospital Medical Center, University of Cincinnati)

  • Xiaoqing Rong-Mullins

    (The Ohio State University, Comprehensive Cancer Center
    The Ohio State University)

  • Jessica Kohlschmidt

    (The Ohio State University, Comprehensive Cancer Center
    The Ohio State University)

  • Kellie J. Archer

    (The Ohio State University, Comprehensive Cancer Center
    The Ohio State University)

  • Michael A. Freitas

    (The Ohio State University, Comprehensive Cancer Center
    The Ohio State University)

  • Yi Zheng

    (Cincinnati Children’s Hospital Medical Center, University of Cincinnati)

  • Robert J. Lee

    (The Ohio State University)

  • Iannis Aifantis

    (New York University School of Medicine)

  • George Vassiliou

    (Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus
    Cambridge University Hospitals NHS Trust)

  • Guramrit Singh

    (The Ohio State University)

  • Sakari Kauppinen

    (Aalborg University)

  • Clara D. Bloomfield

    (The Ohio State University, Comprehensive Cancer Center)

  • Adrienne M. Dorrance

    (The Ohio State University, Comprehensive Cancer Center)

  • Ramiro Garzon

    (The Ohio State University, Comprehensive Cancer Center)

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.

Suggested Citation

  • 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 & M, 2019. "The long non-coding RNA HOXB-AS3 regulates ribosomal RNA transcription in NPM1-mutated acute myeloid leukemia," Nature Communications, Nature, vol. 10(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-13259-2
    DOI: 10.1038/s41467-019-13259-2
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    Cited by:

    1. Yin Liu & Xinyi Liu & Dongyi Wei & Lu Dang & Xiaoran Xu & Shisheng Huang & Liwen Li & Sanyun Wu & Jinxian Wu & Xiaoyan Liu & Wenjun Sun & Wanyu Tao & Yongchang Wei & Xingxu Huang & Kui Li & Xinjie Wan, 2024. "CoHIT: a one-pot ultrasensitive ERA-CRISPR system for detecting multiple same-site indels," Nature Communications, Nature, vol. 15(1), pages 1-14, December.

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