현재 위치：홈 > 뉴스현황 > Press Events > Circular RNA Linked ...
저자： 업로드：2017-08-16 조회수：
Circular RNAs (circRNAs), closed loops of noncoding RNA, drift through the cytoplasm like so many ring buoys floating on the sea. Precisely what the circRNAs are doing there hasn’t been clear. Because they are especially abundant in brain cells, circRNAs have been thought to have a role in brain function, possibly via the regulation of gene expression. This possibility looks more likely than ever, now that a new study indicates that circRNAs, which are stable and long-lived, help preserve relatively fragile microRNAs (miRNAs), and thereby influence brain function.
Scientists based at the Max Delbrück Center (MDC) deliberately depleted cells of circRNA to see what would happen. Specifically, these scientists, led by Nikolaus Rajewsky, Ph.D., deployed CRISPR/Cas9 technology to deprive mice of the gene for Cdr1as, a circRNA known to be predominantly expressed in excitatory neurons. Then the scientists assessed how miRNA expression, electrophysiology, and behavior might be affected.
The expression of most miRNAs remained unperturbed. However, miR-7 was downregulated and miR-671 upregulated. These changes were post-transcriptional, consistent with the idea that Cdr1as usually interacts with these miRNAs in the cytoplasm.
The 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. Also affected were mRNAs that encode proteins involved in the maintenance of the animals' sleep–wake cycles.
Interestingly, the researchers observed increased spontaneous neurotransmitter vesicle release and decreased synaptic responses to two consecutive stimuli. Additional behavioral analyses showed that while mice lacking Cdr1as demonstrated normal social behavior, unaffected anxiety levels, unperturbed locomotor activity, and no deficits in recognition memory, they exhibited impairments in sensory and cognitive processing (called sensorimotor gating)—a deficiency associated with neuropsychiatric disorders.
The MDC scientists detailed their findings August 10 in the journal Science, in an article entitled “Loss of a Mammalian Circular RNA Locus Causes miRNA Deregulation and Affects Brain Function.” This article presents data that—for the first time—link a circRNA to brain function.
“Expression of immediate early
genes such as Fos, a direct
miR-7 target, was enhanced in Cdr1as-d
