title: RNA G-quadruplexes are globally unfolded in eukaryotic cells and depleted in bacteria.
abstract: In vitro, some RNAs can form stable four-stranded structures known as G-quadruplexes. Although RNA G-quadruplexes have been implicated in posttranscriptional gene regulation and diseases, direct evidence for their formation in cells has been lacking. Here, we identified thousands of mammalian RNA regions that can fold into G-quadruplexes in vitro, but in contrast to previous assumptions, these regions were overwhelmingly unfolded in cells. Model RNA G-quadruplexes that were unfolded in eukaryotic cells were folded when ectopically expressed in Escherichia coli; however, they impaired translation and growth, which helps explain why we detected few G-quadruplex-forming regions in bacterial transcriptomes. Our results suggest that eukaryotes have a robust machinery that globally unfolds RNA G-quadruplexes, whereas some bacteria have instead undergone evolutionary depletion of G-quadruplex-forming sequences.
authors.affiliation: Howard Hughes Medical Institute, Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA. Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Junjie U
authors.initials: JU
authors.lastname: Guo
authors.affiliation: Howard Hughes Medical Institute, Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA. Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. dbartel@wi.mit.edu.
authors.forename: David P
authors.initials: DP
authors.lastname: Bartel
mesh_terms: D001419:Bacteria / Q000235:genetics / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D005057:Eukaryotic Cells / Q000378:metabolism*; D054856:G-Quadruplexes; D057809:HEK293 Cells; D006801:Humans; D012313:RNA / Q000737:chemistry*; D059370:RNA Folding; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D013463:Sulfuric Acid Esters / Q000737:chemistry; D059467:Transcriptome
chemical_list: D013463:Sulfuric Acid Esters; D012313:RNA; C007482:dimethyl sulfate