Project description:Activity-dependent protein synthesis is critical for determining changes in dendritic proteomes underlying brain function, yet the mechanisms governing these changes are lacking. Here, we combined proximity-based labeling of dendritic transcriptome, translatome, and proteome to study the dynamics of RNA regulation in activated synapses. We discovered that depolarization leads to a switch from RNAs translated under basal conditions to new translation of previously unrecognized subsets of depolarization-dependent transcripts. Dynamically regulated RNAs bound by specific regulatory proteins, including NOVA1, FMRP, and ELAVLs, rapidly generate proteins with roles in mitochondrial regulation, RNA metabolism, translational control, and synaptic signaling in dendrites. Knockdowns of activity-induced dendritic RNAs altered neuronal physiology, underscoring how dynamic switches in the regulation of RNAs encoding coordinated sets of proteins underlie synaptic plasticity.
Project description:This SuperSeries is composed of the following subset Series: GSE24440: Sprouting transcriptome in cortical neurons: young GSE24441: Sprouting transcriptome in cortical neurons: aged Refer to individual Series
Project description:Activity-dependent protein synthesis is critical for determining changes in dendritic proteomes underlying brain function, yet the mechanisms governing these changes are lacking. Here, we combined proximity-based labeling of dendritic transcriptome, translatome, and proteome to study the dynamics of RNA regulation in activated synapses. We discovered that depolarization leads to a switch from RNAs translated under basal conditions to new translation of previously unrecognized subsets of depolarization-dependent transcripts. Dynamically regulated RNAs bound by specific regulatory proteins, including NOVA1, FMRP, and ELAVLs, rapidly generate proteins with roles in mitochondrial regulation, RNA metabolism, translational control, and synaptic signaling in dendrites. Knockdowns of activity-induced dendritic RNAs altered neuronal physiology, underscoring how dynamic switches in the regulation of RNAs encoding coordinated sets of proteins underlie synaptic plasticity.
Project description:To understand the effect of reducing miR-27b levels on genome-wide expression in cortical neurons and identify potential targets of miR-27b, we generated dissociated cortical neuron cultures and treated them with lentivirus to knock down miR-27b. 2 treatment conditions (control lentivirus or lentivirus to knock down miR-27b); 3 neuronal preparations of dissociated mouse cortical neurons; total of 6 samples