Table 1.

A comparison of the structural and biochemical properties of RNaseL and IRE1, showing similarities and differences.

	Similarities
	RNaseL	IRE1
Inactive state	Monomeric
Active state	Oligomeric
Factor driving oligomerization	Catenation of by 2–5A bound to ankyrin repeats of multiple monomers	Titration of HSPA5 bound to luminal domain and catenation of the same from multiple monomers by unfolded proteins
Activation upon exogenous overexpression	Yes (demonstrated in vitro for RNaseL)
Position of ligand–receptor and RNase domain	N- and C-terminal, respectively
Ribonuclease domain	KEN or kinase-extension homology domain
Role of PK domain in activating RNase	Nucleotide binding, even in absence of hydrolysis, to conserved residue in protein-kinase like domain is necessary for RNase activity (Tirasophon et al., 1998; Dong and Silverman, 1999; Papa et al., 2003; Lin et al., 2007)
Nature of RNase substrates	Both 28S rRNA and mRNAs	IRE1β can cleave both 28S rRNA and mRNA while IRE1α substrates include only mRNAs (Iwawaki et al., 2001)
Dissimilarities
Autophosphorylation	No	Yes
Cleavage substrates	Beside 28S rRNA, predominantly cleaves mRNAs encoding ribosomal proteins (Andersen et al., 2009)	Xbp1u and other mRNAs in addition to microRNA precursors which are targeted as part of the RIDD pathway
Selection of cleavage site	Cleaved between 2nd and 3rd nucleotide positions of UN/N sites (Han et al., 2014)	RNA sequence with the consensus of 5′-CUGCAG-3′ in association with a stem-loop (SL) structure essential for recognition of Xbp1u and other mRNAs (Oikawa et al., 2010)