Chemists Devise a New, Versatile Way to Tag RNA

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Chemists have devised a versatile way to attach handles and tags to RNA so that the tiny molecules can be detected and traced within cells or selectively pulled from a complex mixture of molecules.

RNA, the single-stranded genetic material that carries transcripts of genes from the cell nucleus and guides the assembly of proteins from those templates (among other things), can loop back on itself, forming bonds between its nucleotide bases, to make structures such as hairpin turns.

A research group led by Neal Devaraj, an assistant professor of chemistry and biochemistry at UC San Diego, used a bacterial enzyme that recognizes a specific hairpin turn in RNA to make their tagging system. The enzyme’s natural role is to substitute a molecule called PreQ for a guanine in the open, wobbly loop on the outer curve of the bend.

Using chemical links, they made a system that can attach a variety of molecules to PreQ so that the RNA is tagged with something useful, such as a fluorescent dye or biotin, a kind of molecular handle, and demonstrated its use to purify specific RNAs and to visualize their location within cells.

The system could also be used to substitute artificial nucleotide bases for the design of novel biological systems, they report in the Journal of the American Chemical Society.

Any RNA with this particular hairpin structure, even relatively large transcripts of genes, can be tagged in this way, which should prove useful to a wide range of biochemists and biomedical scientists.

The team has applied for a patent for this new technology. Parties interested in licensing opportunities should contact Skip Cynar in UC San Diego’s technology transfer office at scynar@ucsd.edu or (858) 822-2672.

Additional authors include Seth Alexander, Kayla Busby, Christian Cole and Cun Yu Zhou. The Department of Defense Army Research Office funded this work. Busby was supported by a NSF Graduate Research Fellowship. Tagged RNA within cells was visualized using the confocal microscope at UC San Diego’s shared microscopy facility.