Fig. 5.

PRMT5 is targeted to multiple histone and nuclear targets by cofactors. A cartoon representation of the function of PRMT5 methylation of nuclear proteins (nucleus represented by pale yellow). Methylated substrates are represented with a red “–CH₃”. Histones, the protein component of chromatin, are synthesized and then transported to the nucleus. PRMT5–MEP50 targets newly synthesized histone H2A in the cytoplasm and may target soluble H4 in the nucleus (both H2A and H4 are methylated on R3 in the sequence N-SGRGK… as shown in the cartoon), as well as transcription factors such as p53 and NF-κB. PRMT5-methylated H2A and H4 are then deposited into chromatin (DNA wrapped around histone proteins, with histone N-terminal tails indicated in the cartoon). Alternative binding partners for PRMT5 (RioK1 in the cytoplasm, CoPR5 and Menin in the nucleus) may displace one or more MEP50 molecules and alter the targeting of PRMT5 toward substrates as shown, including histone H3 on R2 or R8 in the sequence N-ARTKQTARKST…