Pharma Focus Asia

University Of California Researchers Develop New Enzyme Linked to Cell Growth, Cancer

The researchers from the University of California have discovered the structure of ZCCHC4, a novel RNA-modifying enzyme.

The cell proliferation is influenced by ZCCHC4 and has been linked to cancers. Apart from this, they also identified the mechanism that controls how the ZCCHC4 enzyme recognises its substrate.

ZCCHC4 introduces an RNA modification known as N6-methyladenosine (m6A) into ribosomes (protein cell organelles made of RNA and proteins).

It was also revealed by the researchers that ZCCHC4 controls both protein synthesis and cell proliferation by bringing these m6A modifications into ribosomes.

Moreover, the ZCCHC4 is overexpressed in samples of hepatocellular carcinoma, the most commonly diagnosed form of primary liver cancer.

Due to the important role m6A plays in RNA metabolism and biology, it has received enormous attention in recent years. However, how it is dynamically programmed and distributed throughout the cell is not well understood.

The researchers first created an enzymatically active ZCCHC4 fragment that was structurally rigid.

They then crystallized this protein structure and performed an x-ray diffraction of the crystals.

This data was analysed, eventually yielding the structure of ZCCHC4.

The research on this novel enzyme was carried by Jikui Song, an associate professor of biochemistry at UC Riverside, Mengjiang Huang, Jiuwei Lu, Wendan Ren, and Linfeng Gao of UC Riverside; and Dongxu Li and Gang Greg Wang of the University of North Carolina at Chapel Hill.

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