MBNL1 regulates essential alternative RNA splicing patterns in MLL-rearranged leukemia

Svetlana S. Itskovich; Arun Gurunathan; Jason Clark; Matthew Burwinkel; Mark Wunderlich; Mikaela R. Berger; Aishwarya Kulkarni; Kashish Chetal; Meenakshi Venkatasubramanian; Nathan Salomonis; Ashish R. Kumar; Lynn H. Lee

doi:10.1038/s41467-020-15733-8

Nature Communications (May 2020)

MBNL1 regulates essential alternative RNA splicing patterns in MLL-rearranged leukemia

Svetlana S. Itskovich,
Arun Gurunathan,
Jason Clark,
Matthew Burwinkel,
Mark Wunderlich,
Mikaela R. Berger,
Aishwarya Kulkarni,
Kashish Chetal,
Meenakshi Venkatasubramanian,
Nathan Salomonis,
Ashish R. Kumar,
Lynn H. Lee

Affiliations

Svetlana S. Itskovich: Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children’s Hospital Medical Center
Arun Gurunathan: Cancer and Blood Diseases Institute, Cincinnati Children’s Hospital Medical Center
Jason Clark: Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children’s Hospital Medical Center
Matthew Burwinkel: Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children’s Hospital Medical Center
Mark Wunderlich: Division of Experimental Hematology and Cancer Biology, Cincinnati Children’s Hospital Medical Center
Mikaela R. Berger: College of Medicine, University of Cincinnati School of Medicine
Aishwarya Kulkarni: Department of Electrical Engineering and Computer Science, University of Cincinnati
Kashish Chetal: Division of Biomedical Informatics, Cincinnati Children’s Hospital Medical Center
Meenakshi Venkatasubramanian: Department of Electrical Engineering and Computer Science, University of Cincinnati
Nathan Salomonis: Division of Biomedical Informatics, Cincinnati Children’s Hospital Medical Center
Ashish R. Kumar: Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children’s Hospital Medical Center
Lynn H. Lee: Department of Pediatrics, University of Cincinnati School of Medicine

DOI: https://doi.org/10.1038/s41467-020-15733-8
Journal volume & issue: Vol. 11, no. 1
pp. 1 – 14

Abstract

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The alternative splicing regulator MBNL1 is overexpressed in MLL-rearranged leukaemia. Here, the authors show that MBNL1-mediated alternative splicing leads to a specific splicing profile in MLL-rearranged leukaemia and loss or inhibition of MBNL1 impairs leukaemia development in vitro and in vivo.

Published in Nature Communications

ISSN: 2041-1723 (Online)
Publisher: Nature Portfolio
Country of publisher: United Kingdom
LCC subjects: Science
Website: https://www.nature.com/ncomms/

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