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| Status |
Public on Jul 07, 2021 |
| Title |
Inducible and reversible inhibition of miRNA-medaited gene repression in vivo |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
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.
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| |
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| Overall design |
RNAseq analysis of gene expression in a panel of tissues from control and t6b expressing mice
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| |
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| Contributor(s) |
Ventura A, Li X, La Rocca G, King B |
| Citation(s) |
34463618 |
| |
| Submission date |
Jul 06, 2021 |
| Last update date |
Oct 06, 2021 |
| Contact name |
Andrea Ventura |
| E-mail(s) |
venturaa@mskcc.org
|
| Phone |
6468883068
|
| Organization name |
Memorial Sloan Kettering Cancer Center
|
| Department |
Cancer Biology and Genetics
|
| Lab |
Ventura
|
| Street address |
408 East 69th, ZRC-1201
|
| City |
New York |
| State/province |
NY |
| ZIP/Postal code |
10065 |
| Country |
USA |
| |
|
| Platforms (2) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
|
| Samples (24)
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| Relations |
| BioProject |
PRJNA744226 |
| SRA |
SRP327199 |
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