Protein arginine methyltransferase 5 (PRMT5) has been implicated as an important regulator of many cellular processes and signaling pathways, including chromatin remodeling, RNA splicing, DNA transcription, and cell proliferation. Therefore, structural and functional studies on PRMT5 are quite important. The full length of PRMT5 gene was cloned into vector pGEX-4T-1, resulting in only low expression levels in Escherichia coli (E. coli). Here, it was showed that the several N-terminal amino acids deletions could result in a significant increase in the amount of soluble fraction, while one of them did not affect the protein-arginine methyltransferase activity. And it was also found that the N-terminal 15 amino acids region of PRMT5 may be important for the catalytic activity.