Sequential inverse dysregulation of the RNA helicases DDX3X and DDX3Y facilitates MYC-driven lymphomagenesis

• Published in: Molecular cell Vol. 81; no. 19; pp. 4059 - 4075.e11
• Main Authors: Gong, Chun, Krupka, Joanna A., Gao, Jie, Grigoropoulos, Nicholas F., Giotopoulos, George, Asby, Ryan, Screen, Michael, Usheva, Zelvera, Cucco, Francesco, Barrans, Sharon, Painter, Daniel, Zaini, Nurmahirah Binte Mohammed, Haupl, Björn, Bornelöv, Susanne, Ruiz De Los Mozos, Igor, Meng, Wei, Zhou, Peixun, Blain, Alex E., Forde, Sorcha, Matthews, Jamie, Khim Tan, Michelle Guet, Burke, G.A. Amos, Sze, Siu Kwan, Beer, Philip, Burton, Cathy, Campbell, Peter, Rand, Vikki, Turner, Suzanne D., Ule, Jernej, Roman, Eve, Tooze, Reuben, Oellerich, Thomas, Huntly, Brian J., Turner, Martin, Du, Ming-Qing, Samarajiwa, Shamith A., Hodson, Daniel J.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 07.10.2021
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Animals; B-cell lymphoma; B-lymphocytes; B-Lymphocytes - enzymology; B-Lymphocytes - pathology; biogenesis; Burkitt lymphoma; Cell Line, Tumor; Child; Child, Preschool; DDX3X; DEAD-box RNA Helicases - genetics; DEAD-box RNA Helicases - metabolism; Endoplasmic Reticulum Stress; Female; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; germinal center; Humans; Loss of Function Mutation; Lymphoma, B-Cell - enzymology; Lymphoma, B-Cell - genetics; Lymphoma, B-Cell - pathology; Male; males; Mice, Transgenic; Middle Aged; Minor Histocompatibility Antigens - genetics; Minor Histocompatibility Antigens - metabolism; mutants; MYC; Neoplasm Proteins - biosynthesis; Neoplasm Proteins - genetics; Protein Biosynthesis; protein synthesis; Proteome; Proteostasis; proteotoxic stress; Proto-Oncogene Proteins c-myc - genetics; Proto-Oncogene Proteins c-myc - metabolism; RNA helicase; RNA helicases; testes; translation; Y chromosome; Young Adult; DDX3X; proteotoxic stress; MYC; Burkitt lymphoma; translation; germinal center; RNA helicase

DDX3X is a ubiquitously expressed RNA helicase involved in multiple stages of RNA biogenesis. DDX3X is frequently mutated in Burkitt lymphoma, but the functional basis for this is unknown. Here, we show that loss-of-function DDX3X mutations are also enriched in MYC-translocated diffuse large B cell...