Table 1.

IR characteristics displayed in Figure 2 that positively regulate IR

Level	Features	Contribution to IR	References
Histone/DNA	H3.3K36me3 Histone modification (magnets)	Chromatin-bound BS69 (via H3.3K36me3-mediated recruitment) interacts with snRNPs including EFTUD2, a component of the U5 small ribonucleoprotein complex, and destabilizes the spliceosome complex. BS69 has also been shown to repress RNA Pol II elongation	(77,88–90)
	Slow RNA Pol II elongation (snail)	Impaired recognition and splicing of constitutive introns	(17,78,163)
DNA	High CpG density/Reduced CpG methylation	Impaired binding of MeCP2 and recruitment of splicing factors to mRNAs	(78,81,84)
	High intronic GC content	Generates DNA secondary structures that increase pausing of RNA Pol II over retained introns	(17,51,59,63)
RNA	Weak splice site(s)	Less effective recognition of canonical splicing sites	(17,53,54)
	Enrichment of RNA associated proteins binding sites in retained intron and flanking exon(s)	Binding of splicing repressors/IR enhancers	(70–72,94,95)
	Short intronic length	Reduce the availability of alternative splice sites and motifs for the binding of splicing factors	(17,51,53,54)
	High intronic GC content	Generates secondary structures that reduce the binding of RNA associated proteins/splicing enhancers	(17,51,59)