PSF and p54nrb/NonO are highly homologous and related proteins. p54nrb/NONO has a region of 320 amino acids with a 71% identity and a 7% similarity to a 320 amino acid region within PSF. Both proteins have both DNA and RNA binding domains, which underlies their multifunctionality. Indeed, these proteins have been implicated in both transcriptional activation and splicing. Both proteins are known to bind to the DNA binding domains of nuclear hormone receptors (such as the thyroid hormone receptor and the retinoid X receptor), and modulate transcriptional activation. These proteins bind to each other, select the same optimal RNA sequence from RNA pools, and have been associated with spliceosomes. Both have been shown to bind to the C-terminal domain of RNA polymerase II, where they may couple pre-mRNA splicing and RNA processing. PSF and NonO enhance Topoisomerase I cleavage of DNA, and induce its jumping to other DNA helices after cleavage. Finally, both have been shown to bind and retain defective and hyperedited mRNAs within the nucleus, preventing translation of mutated proteins.