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RNA Rosetta stone? Molecules' second, structural language predicted from their first, linear one

Rosetta stoneThe RNA whisperer is at it again.

In a study just published in Nature, Stanford's Howard Chang, MD, PhD - an expert in all things RNA - and his colleagues detail how they were able to translate from one language spoken by this versatile biomolecule to another, more obscure but important one.

RNA is best known as the intermediate material in classic protein production. A so-called "messenger RNA" molecule serves as a mobile, short-lived copy of its more durable lookalike, DNA, the stuff genes are made of. Gene-reading machines in a cell's nucleus produce RNA copies of protein-coding genes. Unlike a gene, which is a sequence of chemical letters situated somewhere on a big, bulky chromosome, a messenger RNA molecule can float out of the nucleus to the cell's watery cytoplasm where proteins get made, and transmit a gene's instructions to the protein-making machinery.

But RNA does more than simply specify which proteins are going to get made. A messenger RNA molecule's 3-dimensional shape, for example, conveys bountiful information telling the cell's protein-producing proletariat where to bring it, what to do with it when it gets there, and when and and how much protein to make from it.

DNA is famously double-stranded. That’s because, of its four component chemical "letters,” two in particular share a strong mutual attraction, biophysically speaking. Happily, the other two letters have a chemical crush on one another as well. So, when the letters composing one DNA strand are complementary to those on a closely opposed strand (and they virtually always are), the two strands lock in a lasting embrace to form a stable double helix.

RNA molecules are strings of four different chemical letters almost identical to those constituting DNA. But unlike DNA, an RNA molecule typically travels solo, as a single-stranded chain of those four chemical letters. It is thus a rather playful, floppy molecule. Nonetheless, the same alphabetical affinities that produce DNA’s double helix are at work in an RNA molecule, albeit in a more fleeting form: Small sequences of chemical letters along an RNA molecule find themselves attracted to complementary sequences elsewhere on the same molecule, causing it to fold into so-called secondary structures featuring pinched double-stranded sections alternating with bulges and loops, hairpins and hinges.

Chang's gang has figured out how to predict, based on an RNA molecule's linear chemical sequence, the way it will fold up into its secondary structure. They were able to do this for  thousands of differently shaped RNA molecules found in one type of human cell - about a thousandfold increase over the number of such structures that had been laboriously determined to date, Chang told me. That has consequences for understanding disease mechanisms and, potentially, for drug discovery as well.

Looks like RNA research is shaping up.

Previously: Night of the living dead gene: Pseudogene wakes up, puts chill on inflammation, New job description for RNA, oldest professional biomolecule and iPhone app shows 2D structures of thousands of RNA molecules
Photo by OliBac

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