Introducing the brain: non-coding controls in the brain. (Introduction)

by David Turell , Friday, September 30, 2022, 01:56 (785 days ago) @ David Turell

A menagerie of RNA types:

https://www.the-scientist.com/features/the-noncoding-regulators-of-the-brain-70457?utm_...

" “it was frustrating to see how few protein-coding genes exist,” says Geraldine Zimmer-Bensch, a neuroepigeneticist at Rheinisch-Westfälische Technische Hochschule Aachen in Germany, “and even more frustrating, how little difference there is between the mouse and the human protein-coding genome.” Yes, there are proteins and variants of proteins that are unique to our species, she says, but there simply aren’t enough of them to explain humans’ singular cognitive prowess.

"This was particularly surprising because at least a tenth of the human proteome consists of proteins whose main function is in the brain—some estimates say it’s more like a third.

"According to Zimmer-Bensch and an increasing number of neuroscientists, the missing piece of the puzzle is RNA—specifically, the myriad RNAs that don’t code for proteins, such as long noncoding RNAs (lncRNAs) and microRNAs (miRNAs). Noncoding RNAs are likely protagonists in our brain’s evolutionary story because they are pivotal regulators of gene expression, especially during development, experts say. Changes in traits such as tissue size and shape are easily made by tweaking when and in what cells different proteins are made—precise alterations that generally occur as the result of changes in noncoding regions of the genome, researchers are finding.

"And RNAs aren’t just stars of the evolutionary and developmental past; they are essential for brain functioning now, and evidence is mounting that regulating gene expression is just one of noncoding RNAs’ many neurological tasks....“The functional diversity [of noncoding RNAs] is tremendous and impressive.”

" Moreover, scientists don’t yet have a complete grasp of the total number of RNAs encoded in the genome, and novel RNA forms continue to be discovered. But now, cutting-edge sequencing technologies are giving researchers unprecedented insights into cells, allowing RNA studies to be conducted on the spatial and temporal scales needed for the discipline to begin to catch up to protein biology. And findings from this work are pointing to an inevitable conclusion: RNAs rule the brain.

***

"In addition to finding that miRNA repertoires tend to increase in the genomes of different animal groups over evolutionary time, the team discovered that “there are certain places in evolution where you just had inordinate numbers [of miRNAs] added to a genome,” Peterson says. “And these just happened to coincide with places on the tree where you get these big, obvious jumps in complexity.” This includes a burst of 179 miRNA genes that appeared in the primate lineage after it split from mice.

***

"In a 2018 review on miRNAs and brain development, Kosik and UC San Francisco collaborator Tomasz Nowakowski refer to miRNAs as “an evolutionary cauldron.” Silver, who also did not participate in the research, agreed. “There’s [a] way of thinking that nature reuses strategies that work over and over, and this could be a nice example of that.”

***

"...the expansion and alteration of all kinds of noncoding RNAs were likely essential to brain evolution, he says. “The more complex the species, the bigger the junk DNA or noncoding RNA repertoire is, so that was how evolution climbed the mountain of developmental complexity,” he speculates, adding that “my expectation is they’re all important, that they’re part of a regulatory fabric.”

***

"When it comes to the evolution of human brains specifically, many of the relevant RNAs fall into what are known as human accelerated regions (HARs): stretches of the genome with mutation rates that increased significantly after humans split from chimpanzees (my bold)

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"Long noncoding RNAs (lncRNAs) are generally described as any noncoding RNAs greater than 200 nucleotides in length. Because of their variable size and composition, they can have complex shapes and perform a variety of cellular activities, though most lncRNAs await functional investigation.

"Example: The human and chimpanzee versions of a lncRNA called HAR1 differ by 18 nucleotides, which impacts the molecule’s secondary structure. The human version is predicted to be more stable, but exactly how that translates into differences in brain form or function isn’t yet clear.

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“'It’s sort of like hitting, for lack of a better term, almost a master regulator of gene expression,” says Silver. “And by doing that, it’s going to influence gene expression of its targets likely in a very cell-specific, tissue-specific, timing-specific fashion, and that itself could then affect expression of downstream targets below that.” Because of this, she adds “even though our genomes of human and, say, chimpanzees are remarkably similar globally at the DNA level, there is a whole host of regulatory changes at the RNA level that are likely to contribute synergistically to human-specific traits.'”

Comment. huge article filled with research findings. Why we are not chimps is pretty evident. Note my bold. Human evolution appears driven.