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New study expands understanding of the role of RNA editing in gene control

For many years, scientists thought gene activity was relatively straightforward: Genes were transcribed into messenger RNA, which was processed and translated into the proteins of the body. Certainly, there were many factors governing the transcription process, but gene control happened at the level of the DNA.

In the past few years, however, evidence for a more nuanced understanding of the total genetic system has steadily accumulated. Researchers at The Wistar Institute and elsewhere have been teasing out the details of a process called RNA editing, in which messenger RNA sequence is altered after transcription by editing enzymes, so that a single gene can produce a number of related but distinct variant proteins. Most recently, scientists have discovered an extensive family of small molecules called microRNAs, or miRNAs, that appear to target and inactivate particular messenger RNAs. This targeted gene silencing is now seen as one of the body's primary strategies for regulating its genome.

Now, in a new study published online in Nature Structural & Molecular Biology, a Wistar-led team of scientists details the convergence of these two post-transcriptional genetic systems. The findings show that precursor miRNAs, like messenger RNAs, are themselves subject to specific RNA editing, the result of which is to suppress miRNA expression and its activity. The importance of understanding these joined processes can be seen in the fact that roles have been identified for miRNAs in embryonic development, cell and tissue differentiation, and, increasingly, in cancer formation.

"A couple of years ago, we started to investigate whether miRNA precursors were being edited in processing," says Kazuko Nishikura, Ph.D., senior author on the study and a professor in the gene expression and regulation program at The Wistar Institute. "We found that about half of all miRNA precursor molecules are subject to editing. Looking more closely at a particular miRN
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Source:The Wistar Institute


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