Inducible and reversible inhibition of miRNA-mediated gene repression in vivo
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- Gaspare La Rocca
- Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center
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- Bryan King
- Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center
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- Bing Shui
- Department of Cancer Biology, Dana Farber Cancer Institute
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- Xiaoyi Li
- Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center
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- Minsi Zhang
- Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center
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- Kemal M Akat
- Laboratory of RNA Molecular Biology, The Rockefeller University
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- Paul Ogrodowski
- Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center
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- Chiara Mastroleo
- Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center
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- Kevin Chen
- Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center
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- Vincenzo Cavalieri
- Department of Biological, Chemical and Pharmaceutical Sciences and Technologies, University of Palermo
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- Yilun Ma
- Weill Cornell/Rockefeller/Sloan-Kettering Tri-Institutional MD-PhD Program
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- Viviana Anelli
- Center of Integrative Biology, University of Trento
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- Doron Betel
- Hem/Oncology, Medicine and Institution for Computational Biomedicine, Weill Cornell Medical College
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- Joana Vidigal
- Laboratory of Biochemistry and Molecular Biology, National Cancer Institute
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- Thomas Tuschl
- Laboratory of RNA Molecular Biology, The Rockefeller University
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- Gunter Meister
- Regensburg Center for Biochemistry, University of Regensburg
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- Craig B Thompson
- Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center
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- Tullia Lindsten
- Immunology Program, Memorial Sloan Kettering Cancer Center
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- Kevin Haigis
- Department of Cancer Biology, Dana Farber Cancer Institute
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- Andrea Ventura
- Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center
抄録
<jats:p>Although virtually all gene networks are predicted to be controlled by miRNAs, the contribution of this important layer of gene regulation to tissue homeostasis in adult animals remains unclear. Gain and loss-of-function experiments have provided key insights into the specific function of individual miRNAs, but effective genetic tools to study the functional consequences of global inhibition of miRNA activity in vivo are lacking. Here we report the generation and characterization of a genetically engineered mouse strain in which miRNA-mediated gene repression can be reversibly inhibited without affecting miRNA biogenesis or abundance. We demonstrate the usefulness of this strategy by investigating the consequences of acute inhibition of miRNA function in adult animals. We find that different tissues and organs respond differently to global loss of miRNA function. While miRNA-mediated gene repression is essential for the homeostasis of the heart and the skeletal muscle, it is largely dispensable in the majority of other organs. Even in tissues where it is not required for homeostasis, such as the intestine and hematopoietic system, miRNA activity can become essential during regeneration following acute injury. These data support a model where many metazoan tissues primarily rely on miRNA function to respond to potentially pathogenic events.</jats:p>
収録刊行物
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- eLife
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eLife 10 e70948-, 2021-08-31
eLife Sciences Publications, Ltd