InterPro domain: IPR034168

This entry represents the RNA recognition motif (RRM) of peptidyl-prolyl cis-trans isomerase E (PPIE, also known as Cyp33). PPIE is a nuclear RNA-binding cyclophilin with an N-terminal RNA recognition motif (RRM), and a C-terminal PPIase domain [ 1 ]. Cyp33 possesses RNA-binding activity and preferentially binds to polyribonucleotide polyA and polyU, but hardly to polyG and polyC. It binds specifically to mRNA, which can stimulate its PPIase activity. Moreover, Cyp33 interacts with the third plant homeodomain (PHD3) zinc finger cassette of the mixed lineage leukemia (MLL) proto-oncoprotein and a poly-A RNA sequence through its RRM domain [ 2 ]. It further mediates downregulation of the expression of MLL target genes HOXC8, HOXA9, CDKN1B, and C-MYC, in a proline isomerase-dependent manner [ 3 ]. Cyp33 also possesses a PPIase activity that catalyzes cis-trans isomerization of the peptide bond preceding a proline, which has been implicated in the stimulation of folding and conformational changes in folded and unfolded proteins. The PPIase activity can be inhibited by the immunosuppressive drug cyclosporin A [ 4 ].

1. A new family of cyclophilins with an RNA recognition motif that interact with members of the trx/MLL protein family in Drosophila and human cells. Dev. Genes Evol. 212, 107-13
2. Molecular mechanism of MLL PHD3 and RNA recognition by the Cyp33 RRM domain. J. Mol. Biol. 400, 145-54
3. Pro isomerization in MLL1 PHD3-bromo cassette connects H3K4me readout to CyP33 and HDAC-mediated repression. Cell 141, 1183-94
4. Molecular and biochemical characterization of a protein cyclophilin from the nematode Haemonchus contortus( P ). Parasitol. Res. 96, 199-205