Table 1.

Molecular features of HEPN RNase structures.

Member	Organism	Dimerization	RNase Motif	PDB ID	Citation
CRISPR associated HEPN RNases
Cas13a (or C2C2)	Lachnospiracease bacterium	hetero-dimer	RNdsfH/RNyieH	5WLH, 5W1L,5WIH	(Knott et al., 2017)
	Leptotrichia shahii	hetero-dimer	RNrilH/RNyisH	5WTK, 5WTJ	(Liu et al., 2017)
	Leptotrichia buccalis	hetero-dimer	RNgivH/RNyiaH	5XWY, 5XWP	(Liu et al., 2017)
	Listeria seeligeri	hetero-dimer	RNeiiH/RNnisH	6VRB, 6VRC	(Meeske et al., 2020)
Cas13b	Bergeyella zoohelcum	hetero-dimer	RNfytH/RNkfaH	6AAY	(Zhang et al., 2018)
	Prevotella buccae	hetero-dimer	RNyysH/RNafsH	6DTD	(Slaymaker et al., 2019)
Cas13d	uncultured Ruminococcus sp.	hetero-dimer	RQcvfH/RNciaH	6IV8, 6IV9	(Zhang et al., 2019)
	Eubacterium siraeum	hetero-dimer	RHwcvH/RNtycH	6E9E, 6E9F	(Zhang et al., 2018)
Csm6	Thermus thermophilus	homo-dimer	RNsallvH	5FSH	(Niewoehner and Jinek, 2016)
	Thermococcus onnurineus	homo-dimer	RNylaH	6OV0, 6O71, 6O70, 6O6Z, 6O6Y, 6OSX, 6O6V, 6O6T, 6O6S	(Jia et al., 2019)
	Enterococcus italicus	homo-dimer	RNkvaH	6TUG	(Garcia-Doval et al., 2020)
Csx1	Sulfolobus solfataricus	homo-dimer	RIlyaH	2I71	Structural Genomics
	Pyrococcus furiosus	homo-dimer	RNfiaH	4EOG	(Kim, Kim, and Oh, 2013)
	Sulfolobus islandicus	homo-dimer	RNfiaH	6R9R, 6R7B, 6QZT	(Molina et al., 2019)
Toxin-antitoxin associated HEPN RNases
HepT (or SO_3166)	Shewanella oneidensis	homo-dimer	RNiavH	5YEP, 6M6V, 6W6U, 6M6W, 7BXO	(Yao et al., 2020; Jia et al., 2018)
LsoA	Escherichia coli	hetero-dimer with antitoxin	RHglfH	5HY3	(Wan et al., 2016)
RnlA	Escherichia coli	non-canonical homo-dimer	RHslfH	4I8O	(Wei et al., 2013)
HI0074	Haemophilus influenzae	homo-dimer	RNitsH	1JOG	(Lehmann et al., 2003)
NiKs associated HEPN RNases
Ire1	Saccharomyces cerevisiae	homo-dimer (back-to-back)	RNkyhH	2RIO, 3LJ0, 3LJ1, 3LJ2, 3SDM, 3SDJ, 3FBV, 2BE1*	(Lee et al., 2008; Korennykh et al., 2009; Credle et al., 2005; Wiseman et al., 2010; Korennykh et al., 2011; Korennykh et al., 2011)
	Homo sapiens	homo-dimer (face-to-face)	RNkkhH	2HZ6*, 6HV0, 6URC, 6HX1, 5HGI, 4U6R, 4YZC, 4YZ9, 4YZD, 3P23, 4Z7H, 4Z7G, 6SHC	(Ali et al., 2011; Feldman et al., 2016; Zhou et al., 2006; Colombano et al., 2019; Harnoss et al., 2019; Harrington et al., 2015; Concha et al., 2015; Joshi et al., 2015; Amin-Wetzel et al., 2019)
	Mus musculus	homo-dimer (face-to-face)	RNkkhH	4PL3, 4PL4, 4PL5	(Sanches et al., 2014)
RNase L	Sus scrofa	homo-dimer	RNlgeH	6M11, 6M12, 6M13, 4O1O, 4O1P	(Huang et al., 2014)
	Homo sapiens	homo-dimer	RNlgeH	4OAU, 4OAV	(Han et al., 2014)
RNase PNK	Chaetomium thermophilum	homo-dimer	RHqatH	6OF2, 6OF3, 6OF4	(Pillon et al., 2019)

^*Luminal domain structure of the corresponding cytosolic Ire1 protein kinase-HEPN RNase.