1. A large-scale functional screen identifies Nova1 and Ncoa3 as regulators of neuronal miRNA function
- Author
-
Peter H. Störchel, Simon Sumer, Gabriele Siegel, Juliane Thümmler, Ayla Aksoy-Aksel, Federico Zampa, and Gerhard Schratt
- Subjects
Dendritic spine ,Biology ,General Biochemistry, Genetics and Molecular Biology ,Synapse ,Nuclear Receptor Coactivator 3 ,Rats, Sprague-Dawley ,microRNA ,Neuro-Oncological Ventral Antigen ,Gene silencing ,Animals ,Humans ,News & Views ,Molecular Biology ,Neurons ,Gene knockdown ,General Immunology and Microbiology ,General Neuroscience ,RNA-Binding Proteins ,Argonaute ,Cell biology ,Rats ,MicroRNAs ,HEK293 Cells ,Gene Expression Regulation ,Synaptic plasticity ,Argonaute Proteins ,Function (biology) - Abstract
MicroRNAs (miRNAs) are important regulators of neuronal development, network connectivity, and synaptic plasticity. While many neuronal miRNAs were previously shown to modulate neuronal morphogenesis, little is known regarding the regulation of miRNA function. In a large‐scale functional screen, we identified two novel regulators of neuronal miRNA function, Nova1 and Ncoa3. Both proteins are expressed in the nucleus and the cytoplasm of developing hippocampal neurons. We found that Nova1 and Ncoa3 stimulate miRNA function by different mechanisms that converge on Argonaute (Ago) proteins, core components of the miRNA‐induced silencing complex (miRISC). While Nova1 physically interacts with Ago proteins, Ncoa3 selectively promotes the expression of Ago2 at the transcriptional level. We further show that Ncoa3 regulates dendritic complexity and dendritic spine maturation of hippocampal neurons in a miRNA‐dependent fashion. Importantly, both the loss of miRNA activity and increased dendrite complexity upon Ncoa3 knockdown were rescued by Ago2 overexpression. Together, we uncovered two novel factors that control neuronal miRISC function at the level of Ago proteins, with possible implications for the regulation of synapse development and plasticity.
- Published
- 2014