Premium
A large‐scale functional screen identifies N ova1 and N coa3 as regulators of neuronal mi RNA function
Author(s) -
Störchel Peter H,
Thümmler Juliane,
Siegel Gabriele,
AksoyAksel Ayla,
Zampa Federico,
Sumer Simon,
Schratt Gerhard
Publication year - 2015
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201490643
Subject(s) - biology , microrna , argonaute , microbiology and biotechnology , gene silencing , gene knockdown , dendritic spine , synapse , synaptic plasticity , neuroscience , hippocampal formation , small interfering rna , rna , genetics , gene , receptor
Micro RNA s (mi RNA s) are important regulators of neuronal development, network connectivity, and synaptic plasticity. While many neuronal mi RNA s were previously shown to modulate neuronal morphogenesis, little is known regarding the regulation of mi RNA function. In a large‐scale functional screen, we identified two novel regulators of neuronal mi RNA function, N ova1 and N coa3. Both proteins are expressed in the nucleus and the cytoplasm of developing hippocampal neurons. We found that Nova1 and N coa3 stimulate mi RNA function by different mechanisms that converge on Argonaute ( A go) proteins, core components of the mi RNA ‐induced silencing complex (mi RISC ). While Nova1 physically interacts with Ago proteins, Ncoa3 selectively promotes the expression of A go2 at the transcriptional level. We further show that N coa3 regulates dendritic complexity and dendritic spine maturation of hippocampal neurons in a mi RNA ‐dependent fashion. Importantly, both the loss of mi RNA activity and increased dendrite complexity upon N coa3 knockdown were rescued by A go2 overexpression. Together, we uncovered two novel factors that control neuronal mi RISC function at the level of Ago proteins, with possible implications for the regulation of synapse development and plasticity.