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New studies show how the immune system is associated with cancer




Three researchers at the University of Colorado Cancer Center are part of a team that recently published a treatise that provides new insights into how the immune system is associated with cancer. Quentin Vicens, PhD, Jeffrey Kieft, PhD, and Beat Vögeli, PhD are authors of a paper investigating how an enzyme called ADAR1 functions in cancer-related pathways.

“Intra-cells, ADAR1 edits native RNA (or auto-RNA) so that cells recognize it as their own, which is an important protection against autoimmune diseases,” Kieft said. I will. “But when the virus is infected, the viral RNA is not edited by ADAR1, so the cell can recognize it and react. The cell recognizes the presence of foreign RNA and activates its immune response. Repel the infection. “

About their treatise published in the journal last month Nature Communications, Kieft, Vögeli, Viccens, and other members of the team, including Parker Nichols, a graduate student in the Structural Biology and Biochemistry Program of CU Medical School, who collaborates with Kieft Lab and Vögeli Lab. Did you check? ADAR1 binds to RNA and performs the editing process. They already knew that the domain of ADAR1 known as Z-alpha binds to an RNA form called Z-RNA, but found that Z-alpha ADAR1 could also bind to other RNA forms.

The team asked, “If you don’t think it will form Z-RNA, how are all these places in the RNA recognized by Z-alpha? One of the takeaway messages is another form of RNA. Can bind to Z-alpha ADAR1 and even partially form Z-RNA, as it shows that RNA can form this particular Z structure in previously unrecognized locations. That was a surprise. “

Dr. Jeffrey Kieft, Research Author, CU School of Medicine

The team is currently proposing a model of how Z-alpha ADAR1 binds to different types of RNA. Due to the role of ADAR1 in the regulation of cancer, this is an important finding in cancer research. A functioning immune system can often detect and eliminate cancer cells as dangerous, but if ADAR1 is edited too much, the cells suppress the immune response to protect themselves. There may be.

“Many cancers have ADAR1 up-regulation, which does more than it should,” says Kieft. “Excess ADAR1 will probably lead to more RNA editing than usual. This misregulates things and affects specific regions of RNA or RNA types.

Over-editing will abandon the normal immune response, but it probably has many other effects inside the cell as well. Cancer is a disease that has failed to regulate genes, so if important regulatory pathways, such as those edited by ADAR, fail, it can contribute to cancer. “

Knowing all the targets of ADAR1 in the cell is also the first step towards a more effective treatment, says Kieft. If researchers understand the pathway, they may be able to find ways to disrupt the over-editing process and boost the immune response. This is a finding that also applies to many other illnesses-since the paper was published, researchers have heard from other scientists across the country who are interested in ADAR1, says Vögeli.

“We got a lot of feedback on this treatise,” he says. “Currently, there is a lot of interest in this area, and others are interested in how we can use our structural information.”

Vögeli and Vicens are currently holding a conference focusing on ADAR1 features, compiling special issues in the Journal Molecules and the International Journal of Molecular Sciences.

Vicens states that the research project also demonstrates the importance of collaboration and openness to new directions. “When I joined, I basically brought new projects and directions to the Kieft Lab,” says Vikens. “Both laboratories are open to supporting it intellectually and financially, and the resulting team effort has enabled research that was not done otherwise.”


Journal reference:

Nichols, PJ, et al.. (2021) Recognition of non-CpG repeats of Alu and ribosomal RNA by the Z-RNA binding domain of ADAR1 induces AZ junctions. Nature Communications..


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