RNA structure determination can be performed by liquid state nuclear magnetic resonance (NMR) spectroscopy that requires millimolar amounts of isotopically labeled RNA to obtain well-resolved signals.
A successful approach to generate sufficient isotopically labeled RNA amounts is the in vitro transcription-mediated synthesis of 19F-labeled RNA using fluorinated NTPs. 2F-ATP or 5F-UTP are incorporated instead of their natural counterparts in a non-perturbing way (intact base-pairing properties) and simultaneously function as a sensitive NMR reporter group (larger chemical shift dispersion than 1H).
 Graber et al. (2008) 19F NMR Spectroscopy for the Analysis of RNA Secondary Structure Populations. J. Am. Chem. Soc. 130 (51):17230.
 Sochor et al. (2016) S(19)F-labeling of the adenine H2-site to study large RNAs by NMR spectroscopy. J. Biomol. NMR 64 (1):63.
 Scott et al. (2004) Enzymatic synthesis and 19F NMR studies of 2-fluoroadenine-substituted RNA. J. Am. Chem. Soc. 126 (38):11776.