This article has been reviewed according to Science X's editorial process and policies. Editors have highlighted the following attributes while ensuring the content's credibility: Much like a courier reading an address on a package, neurons must deliver RNA to the precise locations where it is needed. A KAIST research team has discovered how a small chemical modification on RNA acts as a "delivery tag," helping selected RNAs travel to distant regions of neurons.
The findings provide a basis for investigating RNA "delivery errors" in brain disorders—cases in which RNA is produced normally but fails to reach its intended destination—and may ultimately inform the development of new therapeutic strategies. The research team led by professor Ki-Jun Yoon of the Department of Biological Sciences identified the mechanism through which N6-methyladenosine, or m6A, facilitates the transport of specific RNAs to distal axons, the long, cable-like projections of neurons. The study is published in the journal Nature Communications.
Unlike most other cells, neurons have long, highly branched extensions. Axons transmit signals to other neurons, while dendrites receive incoming signals. For the brain to develop and function normally, these structures must grow properly and form appropriate connections.
Because neurons can extend over considerable distances, RNA produced in the cell body may be needed far away, including at the growing tip of an axon. Neurons must therefore identify particular RNAs among thousands of candidates and transport them to the correct subcellular locations. Just as producing a package does not complete its delivery—the package must also reach the correct address—producing RNA is only part of the process.
RNA must arrive at the right place at the right time. However, the mechanisms through which neurons select and transport RNAs over long distances have remained incompletely understood. The research team found that m6A, a small chemical modification added to RNA, plays an important role in this process. m6A is a modification of adenosine, one of the building blocks of RNA, and is known to influence several aspects of RNA metabolism, including stability and translation.
The new study shows that m6A can also function as a molecular "delivery tag" that promotes the transport of specific RNAs to distal regions of neurons. The researchers first examined mice in which Mettl14, a component of the enzyme complex that installs m6A on RNA, was deleted from developing neurons. In the absence of normal m6A modification, the neurons exhibited impaired axon projection and neurite development.
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