RNA Sequences Don’t Predict In Vivo Transcript Structure

Eukaryotes prevent secondary RNA structures called G-quadruplexes, commonly observed in vitro, from forming in the cell.

Written byCatherine Offord

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IN A TWIST: Certain guanine-rich regions of the transcriptome can fold up into four-stranded structures called RNA G-quadruplexes that are thought to have harmful effects in living cells. Both eukaryotes and bacteria have evolved mechanisms to keep these structures unfolded, according to a new study. Eukaryotes likely have protein machinery—possibly helicases to unravel the structure (1) and proteins that bind to the transcripts to keep them from reforming (2). Bacteria appear to have depleted quadruplex-forming sequences from their genomes during their evolution.© KIMBERLY BATTISTA

The paper
J.U. Guo, D.P. Bartel, “RNA G-quadruplexes are globally unfolded in eukaryotic cells and depleted in bacteria,” Science, doi:10.1126/science.aaf5371, 2016.

RNA doesn’t lie flat. Interactions between nucleotides can turn sections of transcripts into loops, bends, and knots, some of which have regulatory functions in the cell. It was with these tangles in mind that Junjie Guo, a postdoc in David Bartel’s lab at MIT, developed an in vitro chemical probe to detect folded regions of RNA. “We were trying to identify all the structures that can stably form in vitro,” he says.

Testing the technique on transcripts extracted from mouse embryonic stem cells, Guo found that one particular conformation was unexpectedly abundant: RNA G-quadruplexes—stable, guanine-rich regions folded into four-stranded structures. “Only dozens of [these] ...

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Meet the Author

Catherine Offord
After undergraduate research with spiders at the University of Oxford and graduate research with ants at Princeton University, Catherine left arthropods and academia to become a science journalist. She has worked in various guises at The Scientist since 2016. As Senior Editor, she wrote articles for the online and print publications, and edited the magazine’s Notebook, Careers, and Bio Business sections. She reports on subjects ranging from cellular and molecular biology to research misconduct and science policy. Find more of her work at her website.
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