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 added to a genome,” Peterson says. “In the last 10 years, the idea that RNAs can have an impact, and that layers of regulation between a DNA and a protein are meaningful, has gotten a lot more attention.”ĭartmouth College paleontologist Kevin Peterson and his colleagues have been studying miRNAs phylogenetically, looking for how changes in miRNA inventories map to evolutionary transitions. This research has led to a shift in understanding of how the brain evolved, Silver says. But it wasn’t until more-recent technological advances, especially in RNA sequencing and single-cell analyses, that scientists could start to study noncoding RNAs in more detail. See full infographic: WEB | PDF Noncoding RNAs as master regulators in brainĪccording to Debra Silver, a developmental neurobiologist at the Duke University School of Medicine in North Carolina, researchers have for nearly half a century been exploring the idea that regions of the genome that don’t encode proteins may play an outsize role in the brain. In a 2022 bioRxiv preprint, researchers uncovered an miRNA repertoire expansion (orange) in the ancestor of coleoid cephalopods-the group that includes squids and octopuses, generally thought to be more intelligent than any other invertebrates-on par with ones seen in the ancestors of vertebrates (blue) and placental mammals (green). Complex Brains Echoed in RNAīursts in microRNA (miRNA) diversity often line up with sudden increases in morphological complexity, especially in the context of the nervous system. And findings from this work are pointing to an inevitable conclusion: RNAs rule the brain. 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. 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. “They’re super selective about when and where they’re expressed,” says Timothy Bredy, a molecular neuroscientist at the University of Queensland in Australia. For one thing, RNA is less stable than both DNA and the proteins they encode, and many RNAs are only expressed at low levels in specific tissues or cells, making them difficult to detect. ![]() Research into how RNAs function in the brain has progressed more slowly than the study of protein function, however. “The functional diversity is tremendous and impressive.” Plus, notes Zimmer-Bensch, noncoding RNAs can be passed from cell to cell via vesicles and junctions. For instance, some noncoding RNAs are actively transported to the ends of axons to play roles completely divorced from gene expression. John Mattick, University of New South WalesĪnd 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.
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