Roles of miRNAs in neuron differentiation and function.

MANUEL DE LA MATA, THI-MINH-PHUC NGUYEN AND WITOLD FILIPOWICZ

Basilea

Simposio; FMI Annual meeting 2009; 2009

Friedrich Miescher Institute for Biomedical Research

Increasing evidence indicates that microRNAs participate in a vast number of biological processes. This is of vital importance to the nervous system which relies on complex gene expression regulatory mechanisms during development and adult functions. While several studies have found miRNA to participate in nervous system development and function, a detailed analysis of the identity, abundance and targets of miRNAs during these processes is missing. We will search for new candidate miRNAs that may affect differentiation of embryonic stem cells towards neurons and in differentiated neurons upon different stimuli. By mechanically isolating dendrites from mature neurons we will profile by deep sequencing miRNAs in dendrites upon neuron stimulation-activity inhibition. Local post-synaptic translation seems to have a particularly important role in the most persistent forms of synaptic plasticity and memory. Several mRNAs are transported along the dendrites as repressed mRNPs and become translated at dendritic spines upon synaptic activation. Up to date a few miRNAs have been implicated in this type of regulation. Additionally, miRNA processing factors and precursor miRNAs have been reported to localize at the synapse, but the potential mechanims involved in local processing are unknown. By tagging miRNA processing proteins we will look for additional evidence that miRNA machinery is localized at dendrite spines and study its dependence with neuron activity.