All neurons begin with the same DNA. Differences arise from which genes they transcribe, or copy, into RNA, molecules that help make proteins. A recent study from MIT shows that individual neurons edit their RNA transcripts at different sites, each at varying rates unique to that cell.
The research focused on tonic and phasic motor neurons in fruit flies, cells that control movement and serve as models for basic brain biology. Researchers surveyed RNA editing across more than 200 single cells. RNA editing changes the sequence of RNA after transcription, often altering the proteins produced or their amounts.
The researchers found hundreds of edits in transcripts from hundreds of genes out of about 15,000 in the fly genome. Many were canonical edits, meaning edits made by the enzyme ADAR, which swaps one RNA building block for another and exists in humans too. Of these, some occurred in protein-coding regions, potentially changing amino acids, the units of proteins. Others were in non-coding areas, which might affect how much protein is made.
Non-canonical edits
The study also uncovered non-canonical edits not done by ADAR, hinting at unknown enzymes that could edit RNA. This could help discover new ways to fix genetic errors in humans, like repairing broken proteins through targeted therapies.
Edits varied widely; some sites were changed over 90 percent of the time, but most ranged from 20 to 70 percent. Neurons of the same type differed in editing, adding individuality. Highly expressed genes, those transcribed a lot, had less editing, as if ADAR could not keep up.
Many edits targeted genes key to neural communication, like those for neurotransmitter release or ion channels that control electrical flow. For instance, Complexin, which regulates glutamate release, had multiple edits affecting synaptic strength. Arc1, involved in synaptic plasticity, showed a non-canonical edit missing in Alzheimer's models.
The researchers have described the methods and results of this study in a paper published in eLife.