Circular RNAs Help to Preserve Fragile MicroRNAs in the Brain
Circular RNAs (circRNAs) exist abundantly in brain cells, but until now the theory that they have a role in brain function has never been confirmed.
A new study highlights the possibility that circRNAs, which are stable and long-lived, help, preserve relatively fragile microRNAs (miRNAs), and thereby influence brain function. In order to discover this, scientists based at the Max Delbrück Centre (MDC) deliberately depleted cells of circRNA to see what would happen. In particular, they deployed CRISPR/Cas9 technology to deprive mice of the gene for Cdr1as, a cricRNA known to be predominantly expressed in excitatory neurons. The scientists then assessed how miRNA expression, electrophysiology, and behaviour might be affected.
The results showed that most miRNAs remained unchanged. However, miR-7 was down-regulated and miR-671 up-regulated. These changes were post-transcriptional, consistent with the idea that Cdr1 as usually interacts with these miRNAs in the cytoplasm.
The evident changes in miRNA concentration had dramatic effects on the messenger RNA (mRNA) and proteins produced by nerve cells, especially for a group called “immediate early genes.” They are part of the first wave of responses when stimuli are presented to neurons. Additionally affected were mRNAs that encode proteins involved in the maintenance of the animals’ sleep-wake cycles.
The researchers witnessed spontaneous neurotransmitter vesicle release and decreased synaptic responses to two consecutive stimuli. Additional behavioural analyses showed that while mice lacking Cdr1 demonstrated normal social behaviour, unaffected anxiety levels, unperturbed locomotor activity, and no deficits in recognition memory, they exhibited impairments in sensory and cognitive processing, a deficiency associated with neuropsychiatric.
The article published in Science, is the first time such a link has been made between circRNA to brain function.