MicroRNA-15/16 Antagonizes Myb To Control NK Cell Maturation.
NK cells develop in the bone marrow and complete their maturation in peripheral organs, but the molecular events controlling maturation are incompletely understood. The miR-15/16 family of microRNA regulates key cellular processes and is abundantly expressed in NK cells. In this study, we identify a critical role for miR-15/16 in the normal maturation of NK cells using a mouse model of NK-specific deletion, in which immature NK cells accumulate in the absence of miR-15/16. The transcription factor c-Myb (Myb) is expressed preferentially by immature NK cells, is a direct target of miR-15/16, and is increased in 15a/16-1 floxed knockout NK cells. Importantly, maturation of 15a/16-1 floxed knockout NK cells was rescued by Myb knockdown. Moreover, Myb overexpression in wild-type NK cells caused a defective NK cell maturation phenotype similar to deletion of miR-15/16, and Myb overexpression enforces an immature NK cell transcriptional profile. Thus, miR-15/16 regulation of Myb controls the NK cell maturation program.
Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110; and.
Ryan P
RP
Sullivan
Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110; and.
Jeffrey W
JW
Leong
Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110; and.
Stephanie E
SE
Schneider
Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110; and.
Aaron R
AR
Ireland
Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110; and.
Melissa M
MM
Berrien-Elliott
Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110; and.
Anvita
A
Singh
Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110; and.
Timothy
T
Schappe
Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110; and.
Brea A
BA
Jewell
Institute of Pharmacology and Toxicology, University of Veterinary Medicine, Vienna 1210, Austria.
Veronika
V
Sexl
Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110; and tfehnige@wustl.edu.
Todd A
TA
Fehniger
D020413:3' Untranslated Regions; D019264:Adoptive Transfer; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D049109:Cell Proliferation / Q000235:genetics; D057809:HEK293 Cells; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000166:cytology* / Q000276:immunology* / Q000637:transplantation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics*; D020598:Proto-Oncogene Proteins c-myb / Q000235:genetics*; D034622:RNA Interference; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D034741:RNA, Small Interfering
D020413:3' Untranslated Regions; D035683:MicroRNAs; C570833:Mirn15 microRNA, mouse; C522604:Mirn16 microRNA, mouse; D020598:Proto-Oncogene Proteins c-myb; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D007371:Interferon-gamma