Microexons are among the smallest pieces of the genome that cells can include in, or skip from, a finished RNA message. A study published in Nature has expanded the catalog of these tiny exons and built a model for predicting how nearby DNA variants may change their use in neurons.
The researchers identified 1,514 human microexons that were missing from two widely used annotation resources. Of those, 292 were spliced differently in neural and non-neural samples, making them candidates for roles that are especially relevant to the nervous system.
A larger map of tiny exons
Microexons are only 3 to 27 nucleotides long. Their size makes them easy to overlook, but including or excluding even such a short sequence can change the protein produced from a gene.
To find more of them, the team analyzed RNA-sequencing data from 4,790 whole-tissue samples, along with 47,380 individual nuclei collected from human cortical regions. About 43% of the newly cataloged microexons appeared in both the bulk-tissue and single-nucleus datasets, giving the researchers two different kinds of evidence for their presence.
The study then used machine learning to identify sequence features that help determine whether neuronal cells include a microexon in RNA. The resulting regulatory model was designed to do more than spot microexons. It also estimated whether a DNA variant near one of them would alter its splicing.
