Inducible and reversible inhibition of miRNA-mediated gene repression in vivo

• DOI: 10.7554/elife.70948
• Publication Date: 2021-08-31T12:01:03Z
• Authors: Gaspare La Rocca; Bryan King; Bing Shui; Xiaoyi Li; Minsi Zhang; Kemal M Akat; Paul Ogrodowski; Chiara Mastroleo; Kevin Chen; Vincenzo Cavalieri; Yilun Ma; Viviana Anelli; Doron Betel; Joana Vidigal; Thomas Tuschl; Gunter Meister; Craig B Thompson; Tullia Lindsten; Kevin Haigis; Andrea Ventura
• Keywords: Homeostasis

Although virtually all gene networks are predicted to be controlled by miRNAs, the contribution of this important layer regulation tissue homeostasis in adult animals remains unclear. Gain and loss-of-function experiments have provided key insights into specific function individual but effective genetic tools study functional consequences global inhibition miRNA activity vivo lacking. Here we report generation characterization a genetically engineered mouse strain which miRNA-mediated repression can reversibly inhibited without affecting biogenesis or abundance. We demonstrate usefulness strategy investigating acute animals. find that different tissues organs respond differently loss function. While is essential for heart skeletal muscle, it largely dispensable majority other organs. Even where not required homeostasis, such as intestine hematopoietic system, become during regeneration following injury. These data support model many metazoan primarily rely on potentially pathogenic events.