Targeting an RNA-Binding Protein Network in Acute Myeloid Leukemia.

Cancer Cell
Eric WangIannis Aifantis

Abstract

RNA-binding proteins (RBPs) are essential modulators of transcription and translation frequently dysregulated in cancer. We systematically interrogated RBP dependencies in human cancers using a comprehensive CRISPR/Cas9 domain-focused screen targeting RNA-binding domains of 490 classical RBPs. This uncovered a network of physically interacting RBPs upregulated in acute myeloid leukemia (AML) and crucial for maintaining RNA splicing and AML survival. Genetic or pharmacologic targeting of one key member of this network, RBM39, repressed cassette exon inclusion and promoted intron retention within mRNAs encoding HOXA9 targets as well as in other RBPs preferentially required in AML. The effects of RBM39 loss on splicing further resulted in preferential lethality of spliceosomal mutant AML, providing a strategy for treatment of AML bearing RBP splicing mutations.

References

Oct 3, 1999·Journal of Medicinal Chemistry·T OwaK Kitoh
Jan 31, 2003·Expert Opinion on Investigational Drugs·Claudiu T Supuran
May 3, 2007·Nature Reviews. Molecular Cell Biology·Bradley M LundeGabriele Varani
Mar 18, 2008·FEBS Letters·Tina GlisovicGideon Dreyfuss
Jul 4, 2008·Trends in Genetics : TIG·Kiven E LukongStéphane Richard
Dec 6, 2008·Blood·Joerg FaberScott A Armstrong
Feb 26, 2009·Cell·Thomas A CooperGideon Dreyfuss
Jun 23, 2009·Biochimica Et Biophysica Acta·Justin R PriggeEdward E Schmidt
Jul 10, 2010·Nature Medicine·Michael G KharasGeorge Q Daley
Nov 3, 2010·Nucleic Acids Research·Kate B CookTimothy R Hughes
Aug 5, 2011·Nature·Johannes ZuberChristopher R Vakoc
Sep 13, 2011·Nature·Kenichi YoshidaSeishi Ogawa
Jan 17, 2012·Nature Structural & Molecular Biology·Olga AnczukówAdrian R Krainer
May 3, 2013·The New England Journal of Medicine·UNKNOWN Cancer Genome Atlas Research NetworkGreg Eley
Dec 18, 2013·Science·Ophir ShalemFeng Zhang
May 6, 2014·The Journal of Biological Chemistry·Sarah LoerchClara L Kielkopf
Oct 20, 2014·Nature Structural & Molecular Biology·Changwei ShaoXiang-Dong Fu
Nov 5, 2014·Nature Reviews. Genetics·Stefanie GerstbergerThomas Tuschl
Mar 20, 2015·Cancer Research·Qianhe ZhouFrank Stegmeier
May 12, 2015·Nature Biotechnology·Junwei ShiChristopher R Vakoc
Sep 17, 2015·The New England Journal of Medicine·Hartmut DöhnerClara D Bloomfield
Mar 15, 2016·The Journal of Clinical Investigation·Jayanth Kumar PalanichamyDinesh S Rao
Apr 7, 2016·Acta Crystallographica. Section D, Structural Biology·Galina A StepanyukJames R Williamson
Jun 11, 2016·Nature Reviews. Cancer·Heidi DvingeRobert K Bradley
Aug 23, 2016·Cell Reports·Koichi R KatsumuraEmery H Bresnick
Sep 1, 2016·The New England Journal of Medicine·François LemonnierTak W Mak
Sep 8, 2016·Nature Medicine·Stanley Chun-Wei Lee, Omar Abdel-Wahab
Oct 28, 2016·Nature·András KotschyOlivier Geneste
Jan 10, 2017·Nature Communications·Cara Lunn ShiraiMatthew J Walter

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Citations

Jan 15, 2020·Cell Cycle·Shannon D ChilewskiJean-Francois Jasmin
Sep 27, 2019·Nature Reviews. Drug Discovery·Joana DesterroMaria Carmo-Fonseca
Apr 3, 2019·Genes, Chromosomes & Cancer·Luise Hartmann, Klaus H Metzeler
Jul 25, 2019·Genes, Chromosomes & Cancer·Justin Taylor, Stanley C Lee
May 14, 2020·Nature Communications·Svetlana S ItskovichLynn H Lee
Feb 12, 2020·Leukemia·David HsiehchenDeepak Nijhawan
Apr 24, 2019·Nature Cell Biology·Maria Guillamot, Iannis Aifantis
Mar 21, 2020·Cancers·Elise AasebøMaria Hernandez-Valladares
Nov 30, 2019·Frontiers in Oncology·Muhammad JamalQiuping Zhang
Apr 19, 2020·Nature Reviews. Clinical Oncology·Sophie C BonnalJuan Valcárcel
May 16, 2020·International Journal of Molecular Sciences·Konstantin SchuschelJessica I Hoell
Jul 5, 2019·EMBO Reports·Manel TariAlexandre Maucuer
Nov 7, 2019·Nature Chemical Biology·Tyler B FaustEric S Fischer
Oct 22, 2020·Nature Reviews. Cancer·Gregory J Goodall, Vihandha O Wickramasinghe
Sep 30, 2020·Molecular and Cellular Biology·Zesen LinRami Khoriaty
Dec 18, 2020·Frontiers in Molecular Biosciences·Xia WuJianzhong Zhang
Oct 16, 2019·Cancer Discovery·Esther A ObengOmar Abdel-Wahab
Nov 26, 2020·British Journal of Pharmacology·Yuewei XuHector C Keun
Oct 17, 2019·Cold Spring Harbor Perspectives in Medicine·Camila Prieto, Michael G Kharas
Nov 6, 2020·Leukemia·Irina A Elcheva, Vladimir S Spiegelman
Feb 4, 2021·Current Opinion in Chemical Biology·Ashley R Julio, Keriann M Backus
Mar 12, 2021·Wiley Interdisciplinary Reviews. RNA·J J David HoPhilip A Marsden
May 14, 2020·Cold Spring Harbor Perspectives in Medicine·Ashwin Kishtagari, Ross L Levine
May 9, 2021·Current Opinion in Pharmacology·Lin ZhangXiaowen Hu

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