Genome complexity: circular DNA in brains (Introduction)

by David Turell , Saturday, August 12, 2017, 01:03 (2662 days ago) @ David Turell

More work reported:

http://www.the-scientist.com/?articles.view/articleNo/50061/title/First-In-Vivo-Functio...

"Using mouse and human postmortem brains, the team showed that miR-7, and to a much lesser extent, another microRNA, miR-671, both bind to Cdr1as.

"Then, the researchers employed CRISPR-Cas9 to delete the locus in mice and create Cdr1as-deficient mutants. Although the knockout animals were outwardly normal—they were viable, fertile, and showed no obvious changes in brain anatomy—the team detected altered levels of free microRNA in areas of the brain where Cdr1as would normally have been expressed: miR-671 was slightly upregulated, while miR-7 levels were markedly lowered—a result that could reflect the circle’s role in preventing degradation of this microRNA by binding to it in wild-type animals, Rajewsky notes.

"Because microRNAs play a role in regulating messenger RNA, the researchers next looked for changes in gene expression in Cdr1as-deficient animals. They found that knockout mice showed altered expression of a set of genes associated with brain activity called immediate early genes—several of which have already been identified as targets of miR-7. “It’s known that neuronal activity is often marked by upregulation of immediate early genes,” Rajewsky says. In the brains of knockout mice, “it was very clear that immediate early genes, as a group, go up.”

"Consistent with this change in gene expression, the researchers found on closer inspection that mutant mice did indeed show abnormalities in neuronal activity. Among other things, single-cell analyses of neurons revealed that, compared to controls, knockout mice had more than double the frequency of miniature excitatory postsynaptic currents—a sign of disrupted neurotransmission.

"Finally, the team ran a suite of experiments to look for behavioral consequences of Cdr1as-deficiency. Although knockout mice exhibited normal anxiety levels and no obvious memory defects, the researchers found that the mutants performed poorly in prepulse inhibition experiments, which measure an animal’s ability to suppress a startle response to an aversive stimulus, such as a sudden loud noise, if a preceding, weaker version of the stimulus has already been played as a warning."

Comment: Just adding another layer of genome complexity in the brain. How much complexity must be shown in the layers of the genome before the need for a designer is recognized?