Table 1.

RNA structure probing methods for both individual RNAs and at the genome-wide scale.

	Experiments	Capabilities	In silico, in vitro, or in vivo	Application	Reaction conditions	Reference
Targeted individual RNA structure probing	NMR; X-ray crystallography; Cryo-electron microscopy	Determine the three-dimensional structure at high resolution	In vitro	Ribosome, HIV	Specific buffer conditions	Lengyel et al., 2014
	Gel-based enzymatic and chemical probing	Determine the RNA secondary structure of high abundant RNAs up to 200 nt length	In vitro or in vivo	E. coli	Specific buffer conditions/cellular conditions	Noller and Chaires, 1972; Zaug and Cech, 1995
	SHAPE-CE	Determine the RNA secondary structure of high abundant RNAs up to 400 nt length	In vitro	Arabidopsis	Specific buffer conditions	Hawkes et al., 2016
	DMS/SHAPE-LMPCR	Determine the RNA secondary structure of low abundant RNAs	In vivo	Arabidopsis, human	Cellular conditions	Kwok et al., 2013
	SHAPE-Seq	Determine the RNA secondary structure of long RNAs	In vitro	RNase P pT181 sense RNA	Specific buffer conditions	Lucks et al., 2011
	SHAPE-MaP; DMS-MaP	Determine the RNA secondary structure of low abundant and long RNAs	In vitro or in vivo	TPP, HIV Yeast, human	Specific buffer conditions/cellular conditions	Siegfried et al., 2014; Smola et al., 2016; Zubradt et al., 2017
Genome-wide RNA structure profiling	FragSeq; PARS; PARTE; PIP-seq	Determine genome-wide in vitro RNA secondary structure with enzymatic probing	In vitro	Mouse Yeast, human Arabidopsis	Specific buffer conditions	Kertesz et al., 2010; Underwood et al., 2010; Li et al., 2012b; Wan et al., 2012, 2014; Gosai et al., 2015; Foley and Gregory, 2016
	CIRS-seq	Determine genome-wide in vitro RNA secondary structure with chemical probing	In vitro	Mouse	Specific buffer conditions	Incarnato et al., 2014
	DMS-seq; Structure-seq; Mod-seq	Determine genome-wide in vivo RNA secondary structure with chemical probing	In vivo	Arabidopsis Yeast Oryza sativa	Cellular conditions	Ding et al., 2014; Rouskin et al., 2014; Talkish et al., 2014; Deng et al., 2018
	icSHAPE	Determine genome-wide in vivo RNA secondary structure with chemical probing	In vivo	Mouse	Cellular conditions	Spitale et al., 2015