Non-coding regions of the genome - those that don't code for proteins - are now known to include important elements that regulate gene activity. Among those elements are microRNAs, tiny, recently discovered RNA molecules that suppress gene expression.
Increasing evidence indicates a role for microRNAs in the developing nervous system, and researchers from Children's Hospital Boston now demonstrate that one microRNA affects the development of synapses - the points of communication between brain cells that underlie learning and memory. The findings appear in the January 19th issue of Nature.
"This paper provides the first evidence that microRNAs have a role at the synapse, allowing for a new level of regulation of gene expression," says senior author Michael Greenberg, PhD, Director of Neuroscience at Children's Hospital Boston. "What we've found is a new mechanism for regulating brain function."
The brain's ability to form and refine synapses allows organisms to learn and respond to their environment, strengthening important synaptic connections, forming new ones, and allowing unimportant ones to weaken. Experiments in Greenberg's lab, done in rats, showed that a microRNA called miR-134 regulates the size of dendritic spines, the protrusions from a neuron's dendrites where synapses form. When neurons were exposed to miR-134, spine volume significantly decreased, weakening the synapse. When miR-134 was inhibited, spines increased in size, strengthening the synapse.
Further experiments showed that miR-134 acts by inhibiting expression of a gene called Limk1, which causes dendritic spines to grow. When neurons were exposed to a growth factor known as brain-derived neurotrophic factor (BDNF), this inhibition was overcome and Limk1 became active again, enhancing spine growth.