La Rocca, Gaspare and King, Bryan and Shui, Bing and Li, Xiaoyi and Zhang, Minsi and Akat, Kemal M. and Ogrodowski, Paul and Mastroleo, Chiara and Chen, Kevin and Cavalieri, Vincenzo and Ma, Yilun and Anelli, Viviana and Betel, Doron and Vidigal, Joana and Tuschl, Thomas and Meister, Gunter and Thompson, Craig B. and Lindsten, Tullia and Haigis, Kevin and Ventura, Andrea (2021) Inducible and reversible inhibition of miRNA-mediated gene repression in vivo. ELIFE, 10: e70948. ISSN 2050-084X
Full text not available from this repository. (Request a copy)Abstract
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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | SMALL INTERFERING RNAS; GW182 PROTEINS; MICRORNA BIOGENESIS; MAMMALIAN MICRORNAS; TARGET RECOGNITION; DICER; EXPRESSION; COMPLEXES; PATHWAY; DROSHA; microRNA; RISC; argonaute; T6B; miRISC; TNRC6; Mouse |
| Subjects: | 500 Science > 540 Chemistry & allied sciences 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Biochemie, Genetik und Mikrobiologie > Lehrstuhl für Biochemie I > Prof. Dr. Gunter Meister |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 13 Sep 2022 06:29 |
| Last Modified: | 13 Sep 2022 06:29 |
| URI: | https://pred.uni-regensburg.de/id/eprint/47775 |
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