Breakthrough Discovery of Key Enzyme’s Role in RNA Modification and Cancer
Researchers at the University of California, Riverside have uncovered the inner workings of a novel RNA-modifying enzyme known as ZCCHC4. This enzyme, crucial for protein synthesis, holds promise for targeted cancer therapies and sheds light on fundamental biological mechanisms.
ZCCHC4, a key player in cell proliferation and implicated in cancer development, has been identified as a unique catalyst for N6-methyladenosine (m6A) modification within ribosomes, the cellular structures responsible for protein synthesis. The groundbreaking study, published in Nature Communications, delves into the intricate regulatory mechanisms governing RNA modification.
Lead researcher, Associate Professor Jikui Song of UC Riverside’s Department of Biochemistry, underscores the significance of ZCCHC4’s role, saying that the findings reveal how ZCCHC4 orchestrates protein synthesis and cell proliferation by introducing m6A modifications into ribosomes. Notably, ZCCHC4’s overexpression has been linked to hepatocellular carcinoma, the most prevalent form of liver cancer.
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For the first time, researchers have elucidated the crystal structure of ZCCHC4, a milestone with far-reaching implications for cancer treatment and our understanding of RNA biology. Song added that this breakthrough has enabled them to explore structure-based drug design strategies against cancers. Moreover, it provides insights into the mechanisms underlying m6A modification, a process integral to various biological functions.
While m6A modification has garnered significant attention for its role in RNA metabolism, the dynamic programming of this modification within cells remains poorly understood. Professor Song’s team’s discovery sheds light on ZCCHC4’s specificity towards targeting ’28S ribosomal RNA,’ an essential component in ribosomal function. The enzyme’s regulation through an ‘autoinhibitory’ mechanism unveils a common regulatory strategy across cellular processes.
The researchers meticulously engineered an enzymatically active ZCCHC4 fragment, coaxing it to crystallize, and analyzed the resulting data using X-ray diffraction techniques.
This accomplishment builds upon the team’s prior success in elucidating the crystal structure of an enzyme involved in DNA methylation, another crucial process in cellular biology.
Looking ahead, the research team aims to explore deeper into the intricate landscape of DNA and RNA modifications, offering promising avenues for understanding disease mechanisms and developing targeted therapeutics.
The collaborative efforts of researchers Wendan Ren, Jiuwei Lu, Mengjiang Huang, and Linfeng Gao from UC Riverside, along with Dongxu Li and Gang Greg Wang from the University of North Carolina at Chapel Hill, were instrumental in this groundbreaking research.
This pioneering work was made possible through generous support from grants provided by the National Institutes of Health, underscoring the vital role of funding in advancing scientific discovery.
