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RNA self-editing: “It sounds simple, but in real life it was really complicated”

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RNA molecule
RNA molecule graphic/Feldman, Wikipedia

From Kelly Rae Chi at Nature:

n 2004, oncologist Gideon Rechavi at Tel Aviv University in Israel and his colleagues compared all the human genomic DNA sequences then available with their corresponding messenger RNAs — the molecules that carry the information needed to make a protein from a gene. They were looking for signs that one of the nucleotide building blocks in the RNA sequence, called adenosine (A), had changed to another building block called inosine (I). This ‘A-to-I editing’ can alter a protein’s coding sequence, and, in humans, is crucial for keeping the innate immune response in check. “It sounds simple, but in real life it was really complicated,” Rechavi recalls. “Several groups had tried it before and failed” because sequencing mistakes and single-nucleotide mutations had made the data noisy. But using a new bioinformatics approach, his team uncovered thousands of sites in the transcriptome — the complete set of mRNAs found in an organism or cell population — and later studies upped the number into the millions1.

Inosine is something of a special case: researchers can readily detect this chink in the armour by comparing DNA and RNA sequences. But at least one-quarter of our mRNAs harbour chemical tags — decorations to the A, C, G and U nucleotides — that are invisible to today’s sequencing technologies. (Similar chemical tags, called epigenetic markers, are also found on DNA.) Researchers aren’t sure what these chemical changes in RNA do, but they’re trying to find out.

That said, epitranscriptomics researchers are excited about the direction their field is taking. “Just as you wouldn’t think of DNA without thinking about how DNA is packaged, or epigenetically modified,” says geneticist Chris Mason at Weill Cornell Medical College in New York City, who has led m6A-mapping efforts, “I think now and in the future, no one will think of RNA without thinking ‘How is it modified?’” target=”another”>More.

As RNA joins DNA as an immensely complex language, information theory is likely to become more important and simplistic Darwinian thinking much less so. But don’t expect to hear the matter put plainly.

See also: Junk RNA helps embryos sort themselves out

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