{"id":193585,"date":"2025-12-15T21:50:08","date_gmt":"2025-12-15T21:50:08","guid":{"rendered":"https:\/\/www.newsbeep.com\/ie\/193585\/"},"modified":"2025-12-15T21:50:08","modified_gmt":"2025-12-15T21:50:08","slug":"rna-editing-study-finds-many-ways-for-neurons-to-diversify-mit-news","status":"publish","type":"post","link":"https:\/\/www.newsbeep.com\/ie\/193585\/","title":{"rendered":"RNA editing study finds many ways for neurons to diversify | MIT News"},"content":{"rendered":"

All starting from the same DNA, neurons ultimately take on individual characteristics in the brain and body. Differences in which genes they transcribe<\/a> into RNA help determine which type of neuron they become, and from there, a new MIT study shows, individual cells edit a selection of sites in those RNA transcripts, each at their own widely varying rates.<\/p>\n

The new study surveyed the whole landscape of RNA editing in more than 200 individual cells commonly used as models of fundamental neural biology: tonic and phasic motor neurons of the fruit fly. One of the main findings is that most sites were edited at rates between the \u201call-or-nothing\u201d extremes many scientists have assumed based on more limited studies in mammals, says senior author Troy Littleton<\/a>, the Menicon Professor in the MIT departments of Biology and Brain and Cognitive Sciences. The resulting dataset and open-access analyses, recently published in eLife<\/a>, set the table for discoveries about how RNA editing affects neural function and what enzymes implement those edits.<\/p>\n

\u201cWe have this \u2018alphabet\u2019 now for RNA editing in these neurons,\u201d Littleton says. \u201cWe know which genes are edited in these neurons, so we can go in and begin to ask questions as to what is that editing doing to the neuron at the most interesting targets.\u201d<\/p>\n

Andres Crane PhD \u201924, who earned his doctorate in Littleton\u2019s lab based on this work, is the study\u2019s lead author.<\/p>\n

From a genome of about 15,000 genes, Littleton and Crane\u2019s team found, the neurons made hundreds of edits in transcripts from hundreds of genes. For example, the team documented \u201ccanonical\u201d edits of 316 sites in 210 genes. Canonical means that the edits were made by the well-studied enzyme ADAR, which is also found in mammals, including humans. Of the 316 edits, 175 occurred in regions that encode the contents of proteins. Analysis indeed suggested 60 are likely to significantly alter amino acids. But they also found 141 more editing sites in areas that don\u2019t code for proteins but instead affect their production, which means they could affect protein levels, rather than their contents.<\/p>\n

The team also found many \u201cnon-canonical\u201d edits that ADAR didn\u2019t make. That\u2019s important, Littleton says, because that information could aid in discovering more enzymes involved in RNA editing, potentially across species. That, in turn, could expand the possibilities for future genetic therapies.<\/p>\n

\u201cIn the future, if we can begin to understand in flies what the enzymes are that make these other non-canonical edits, it would give us broader coverage for thinking about doing things like repairing human genomes where a mutation has broken a protein of interest,\u201d Littleton says.<\/p>\n

Moreover, by looking specifically at fly larvae, the team found many edits that were specific to juveniles, versus adults, suggesting potential significance during development. And because they looked at full gene transcripts of individual neurons, the team was also able to find editing targets that had not been cataloged before.<\/p>\n

Widely varying rates<\/p>\n

Some of the most heavily edited RNAs were from genes that make critical contributions to neural circuit communication such as neurotransmitter release, and the channels that cells form to regulate the flow of chemical ions that vary their electrical properties. The study identified 27 sites in 18 genes that were edited more than 90 percent of the time.<\/p>\n

Yet neurons sometimes varied quite widely in whether they would edit a site, which suggests that even neurons of the same type can still take on significant degrees of individuality.<\/p>\n

\u201cSome neurons displayed ~100 percent editing at certain sites, while others displayed no editing for the same target,\u201d the team wrote in eLife.\u00a0\u201cSuch dramatic differences in editing rate at specific target sites is likely to contribute to the heterogeneous features observed within the same neuronal population.\u201d<\/p>\n

On average, any given site was edited about two-thirds of the time, and most sites were edited within a range well between all-or-nothing extremes.<\/p>\n

\u201cThe vast majority of editing events we found were somewhere between 20 percent and 70 percent,\u201d Littleton says. \u201cWe were seeing mixed ratios of edited and unedited transcripts within a single cell.\u201d<\/p>\n

Also, the more a gene was expressed, the less editing it experienced, suggesting that ADAR could only keep up so much with its editing opportunities.<\/p>\n

Potential impacts on function<\/p>\n

One of the key questions the data enables scientists to ask is what impact RNA edits have on the function of the cells. In a 2023 study<\/a>, Littleton\u2019s lab began to tackle this question by looking at just two edits they found in the most heavily edited gene: complexin. Complexin\u2019s protein product restrains release of the neurotransmitter glutamate, making it a key regulator of neural circuit communication. They found that by mixing and matching edits, neurons produced up to eight different versions of the protein with significant effects on their glutamate release and synaptic electrical current. But in the new study, the team reports 13 more edits in complexin that are yet to be studied.<\/p>\n

Littleton says he\u2019s intrigued by another key protein, called Arc1, that the study shows experienced a non-canonical edit. Arc is a vitally important gene in \u201csynaptic plasticity,\u201d which is the property neurons have of adjusting the strength or presence of their \u201csynapse\u201d circuit connections in response to nervous system activity. Such neural nimbleness is hypothesized to be the basis of how the brain can responsively encode new information in learning and memory. Notably, Arc1 editing fails to occur in fruit flies that model Alzheimer\u2019s disease.<\/p>\n

Littleton says the lab is now working hard to understand how the RNA edits they\u2019ve documented affect function in the fly motor neurons.<\/p>\n

In addition to Crane and Littleton, the study\u2019s other authors are Michiko Inouye and Suresh Jetti.<\/p>\n

The National Institutes of Health, The Freedom Together Foundation, and The Picower Institute for Learning and Memory provided support for the study.<\/p>\n","protected":false},"excerpt":{"rendered":"All starting from the same DNA, neurons ultimately take on individual characteristics in the brain and body. Differences…\n","protected":false},"author":2,"featured_media":193586,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[7],"tags":[103584,103590,103586,103587,103588,61,60,99510,103581,45965,103585,103583,103582,82,103589,60020],"class_list":{"0":"post-193585","1":"post","2":"type-post","3":"status-publish","4":"format-standard","5":"has-post-thumbnail","7":"category-science","8":"tag-adar","9":"tag-andres-crane","10":"tag-cellular-and-molecular-biology","11":"tag-complexin","12":"tag-glutamate-release","13":"tag-ie","14":"tag-ireland","15":"tag-mit-bcs","16":"tag-mit-biology","17":"tag-mit-picower-institute","18":"tag-non-canonical-edits","19":"tag-rna-editing","20":"tag-rna-transcripts","21":"tag-science","22":"tag-synaptic-plasticity","23":"tag-troy-littleton"},"_links":{"self":[{"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/posts\/193585","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/comments?post=193585"}],"version-history":[{"count":0,"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/posts\/193585\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/media\/193586"}],"wp:attachment":[{"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/media?parent=193585"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/categories?post=193585"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/tags?post=193585"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}