Context-specific regulation of cell survival by a miRNA-controlled BIM rheostat.

Autor:	Labi V; Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin-Buch 13125, Germany.; Program of Cellular and Molecular Medicine, Children's Hospital, and Immune Disease Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.; Division of Developmental Immunology, Biocenter, Medical University of Innsbruck, Innsbruck 6020, Austria., Peng S; Program of Cellular and Molecular Medicine, Children's Hospital, and Immune Disease Institute, Harvard Medical School, Boston, Massachusetts 02115, USA., Klironomos F; Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin-Buch 13125, Germany.; Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin-Buch 13125, Germany., Munschauer M; Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin-Buch 13125, Germany.; Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin-Buch 13125, Germany., Kastelic N; Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin-Buch 13125, Germany.; Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin-Buch 13125, Germany., Chakraborty T; Program of Cellular and Molecular Medicine, Children's Hospital, and Immune Disease Institute, Harvard Medical School, Boston, Massachusetts 02115, USA., Schoeler K; Division of Developmental Immunology, Biocenter, Medical University of Innsbruck, Innsbruck 6020, Austria., Derudder E; Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin-Buch 13125, Germany.; Program of Cellular and Molecular Medicine, Children's Hospital, and Immune Disease Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.; Institute for Biomedical Ageing Research, University of Innsbruck, Innsbruck 6020, Austria., Martella M; Institute of Pathology and Neuropathology and Comprehensive Cancer Center Tübingen, Eberhard-Karls-University, Tübingen 72076, Germany., Mastrobuoni G; Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin-Buch 13125, Germany.; Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin-Buch 13125, Germany., Hernandez-Miranda LR; Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin-Buch 13125, Germany., Lahmann I; Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin-Buch 13125, Germany., Kocks C; Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin-Buch 13125, Germany.; Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin-Buch 13125, Germany., Birchmeier C; Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin-Buch 13125, Germany., Kempa S; Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin-Buch 13125, Germany.; Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin-Buch 13125, Germany., Quintanilla-Martinez de Fend L; Institute of Pathology and Neuropathology and Comprehensive Cancer Center Tübingen, Eberhard-Karls-University, Tübingen 72076, Germany., Landthaler M; Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin-Buch 13125, Germany.; Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin-Buch 13125, Germany., Rajewsky N; Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin-Buch 13125, Germany.; Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin-Buch 13125, Germany., Rajewsky K; Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin-Buch 13125, Germany.; Program of Cellular and Molecular Medicine, Children's Hospital, and Immune Disease Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
Jazyk:	angličtina
Zdroj:	Genes & development [Genes Dev] 2019 Dec 01; Vol. 33 (23-24), pp. 1673-1687. Date of Electronic Publication: 2019 Nov 07.
DOI:	10.1101/gad.330134.119
Abstrakt:	Knockout of the ubiquitously expressed miRNA-17∼92 cluster in mice produces a lethal developmental lung defect, skeletal abnormalities, and blocked B lymphopoiesis. A shared target of miR-17∼92 miRNAs is the pro-apoptotic protein BIM, central to life-death decisions in mammalian cells. To clarify the contribution of miR-17∼92:Bim interactions to the complex miR-17∼92 knockout phenotype, we used a system of conditional mutagenesis of the nine Bim 3' UTR miR-17∼92 seed matches. Blocking miR-17∼92:Bim interactions early in development phenocopied the lethal lung phenotype of miR-17∼92 ablation and generated a skeletal kinky tail. In the hematopoietic system, instead of causing the predicted B cell developmental block, it produced a selective inability of B cells to resist cellular stress; and prevented B and T cell hyperplasia caused by Bim haploinsufficiency. Thus, the interaction of miR-17∼92 with a single target is essential for life, and BIM regulation by miRNAs serves as a rheostat controlling cell survival in specific physiological contexts. (© 2019 Labi et al.; Published by Cold Spring Harbor Laboratory Press.)
Databáze:	MEDLINE
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