What Is the HuR Gene and Its Role in the Body?

The gene known as ELAVL1 produces a protein called Human antigen R, or HuR. This protein belongs to a class of regulators that do not alter the genetic code itself, but instead influence how the instructions encoded in genes are used.

HuR is an RNA-binding protein, meaning its primary job is to interact with ribonucleic acid (RNA). It influences the fate of messenger RNA (mRNA), the temporary copy of a gene’s instructions that serves as a direct template for building a protein. By controlling which mRNA molecules persist and are used for protein production, HuR has a broad impact on many cellular functions.

How HuR Governs Gene Expression

The primary function of HuR revolves around its ability to bind to specific sections of messenger RNA (mRNA) molecules. These binding sites, known as AU-rich elements (AREs), are located in a part of the mRNA strand called the 3′ untranslated region (3′-UTR). AREs often act as signals that mark an mRNA molecule for rapid destruction, a normal process that helps cells control the amount of protein being produced.

When HuR attaches to an ARE, it shields the mRNA from cellular machinery that would otherwise break it down. This stabilization extends the lifespan of the mRNA molecule within the cell’s cytoplasm, where proteins are made. A longer-lasting mRNA template means that more protein can be synthesized from it, increasing the expression of that particular gene.

This regulatory action is not static; HuR moves between the cell’s nucleus and the cytoplasm to perform its duties. It first binds to its target mRNAs within the nucleus, where the RNA is initially produced. Subsequently, HuR facilitates the transport of this mRNA-protein complex into the cytoplasm where it continues to protect the mRNA. Once there, it can also directly influence how efficiently the protein-building machinery, the ribosome, translates the mRNA’s code.

Essential Roles of HuR in a Healthy Body

In a healthy state, HuR’s ability to fine-tune gene expression is important for maintaining cellular balance and responding to environmental cues. One of its documented roles is in the cellular stress response. When cells are exposed to damaging stimuli, such as ultraviolet (UV) radiation, HuR accumulates in the cytoplasm and stabilizes the mRNAs of proteins involved in DNA repair and cell survival.

The protein also participates in regulating normal cell growth, division, and differentiation. It influences the expression of cyclins, a group of proteins that guide a cell through the different phases of its life cycle, ensuring that cells divide in an orderly manner. HuR is also involved in the proper functioning of the immune system by modulating the expression of inflammatory proteins. It helps control the stability of mRNAs for cytokines, which are signaling molecules that immune cells use to communicate.

This regulatory function extends to progenitor cells, which are early descendants of stem cells. HuR promotes the survival of these developing cells by stabilizing the mRNA of Mdm2, a protein that keeps a check on the cell death-inducing protein p53. By managing the levels of these proteins, HuR ensures that various biological processes unfold correctly, contributing to tissue maintenance and overall organismal health.

The HuR Gene’s Connection to Disease

While the function of HuR is necessary for normal cellular activity, its dysregulation is associated with several diseases, most notably cancer. In many types of cancer, including breast, colon, and lung cancer, tumor cells show significantly higher levels of HuR, particularly in the cytoplasm. This overexpression is not a benign change; it actively contributes to the malignant properties of the cancer cells.

Elevated HuR in tumors leads to the increased stability of mRNAs that code for proteins driving cancer progression. For instance, HuR can stabilize the mRNA for vascular endothelial growth factor (VEGF), a protein that promotes angiogenesis, the formation of new blood vessels that tumors need to grow. It also stabilizes mRNAs for proteins involved in cell proliferation, such as certain cyclins and proto-oncogenes like c-Fos and c-Myc, helping cancer cells to divide uncontrollably.

HuR can help tumors evade the immune system and become resistant to therapies. It can stabilize mRNAs that encode proteins that suppress T-cell activity or that are involved in metastasis, the process by which cancer spreads to other parts of the body. Beyond cancer, the dysregulation of HuR is also implicated in chronic inflammatory conditions by stabilizing the mRNAs of pro-inflammatory cytokines like TNF-α, which can contribute to the sustained inflammation seen in diseases such as rheumatoid arthritis.

Exploring HuR as a Therapeutic Target

Given its role in promoting cancer and chronic inflammation, the scientific community has identified HuR as a promising target for new therapies. Its frequent overexpression in tumor tissues compared to normal tissues makes it an attractive candidate for drugs that could selectively act on diseased cells. The goal of these therapeutic strategies is to interfere with HuR’s function, thereby reducing the production of proteins that drive disease.

Researchers are exploring several approaches to inhibit HuR. One strategy involves the development of small-molecule inhibitors designed to block HuR from binding to the AU-rich elements on its target mRNAs. If HuR cannot attach to the mRNA, the message will be rapidly degraded, shutting down the production of the harmful protein. Compounds such as MS-444 and others labeled KH-3 have shown promise in preclinical models by successfully impairing this interaction and inhibiting tumor growth.

Another approach aims to prevent HuR from moving from the nucleus to the cytoplasm, trapping it where it cannot stabilize its target mRNAs. Developing drugs that target RNA-binding proteins like HuR presents challenges. These proteins often have complex structures without the well-defined binding pockets that are ideal for drug design, making it difficult to create highly specific inhibitors that do not cause unintended side effects.