麻豆视频

CU Boulder researcher Edward Chuong recently received an international award for his lab鈥檚 work studying transposons in the human genome

Our genome, it turns out, is full of freeloaders鈥攕elfish elements that behave like viruses, because they exist to copy and paste themselves, but unlike viruses, they can鈥檛 leave the cell.

Called transposons, they compose about 50% of the human genome. In fact, most life on Earth contains transposons in their genomes and scientists theorize that transposons have existed since the early beginnings of life on this planet.

However, just because transposons can鈥檛 leave a cell doesn鈥檛 mean they鈥檙e merely 鈥渏unk DNA鈥� or bugs in the genetic code that can鈥檛 affect the cell. Edward Chuong, an assistant professor of molecular, cellular and developmental biology at the 麻豆视频, has found that transposons play a role in the human immune system and how cells communicate within it.

Chuong recently was recognized for this work by the International Cytokine & Interferon Society with听the . The award will be presented in October at the conference in Athens, Greece.

Chuong and his research colleagues in the Chuong Lab have studied how transposons can affect signaling by interferons, which are proteins produced by many types of cells in response to infection. They found that transposons can both help and hinder the interferon response of cells.

鈥淥ne way to think about transposons is they鈥檙e inherently parasites that can occasionally be domesticated to help their hosts,鈥� Chuong says. 鈥淲e found in certain cells that when we deleted the transposon but not the gene, we broke the function necessary for an antiviral response. We showed that cells could no longer respond to a virus because they were missing this transposon, which was an interesting twist to the evolutionary arms race against disease. We鈥檙e starting to see we鈥檝e gotten some help from very old viral infections to fight new ones.鈥�

Not all junk DNA

Chuong and his colleagues have extensively studied endogenous retroviruses, a type of transposon originating from past retroviral infections. A retrovirus, one of which is HIV, is a type of RNA virus that has a special enzyme to convert its genetic information into DNA. When it invades a cell, it can insert that DNA into the host cell鈥檚 DNA and fundamentally change its genome. When this happens to cells that give rise to sperm or egg cells, the retrovirus can become a part of the next generation鈥檚 genome.

They identified MER41, an ancient retrovirus that invaded the genomes of humans鈥� primate ancestors more than 50 million years ago and found that it had been 鈥渄omesticated鈥� to regulate important immune-defense genes, including the antiviral gene AIM2.

鈥淚f we consider that key parts of our DNA are not human in origin, it implies that we are all genetically modified organisms, being changed in important ways by ancient transposons and viruses,鈥� Chuong says. 鈥淲hat we think of as 鈥榟uman鈥� DNA is likely to be less than half of the human genome sequence. Throughout our evolutionary history, transposons have been invading and replicating within our genome, and eventually going extinct. Yet, each invasion leaves behind a 鈥榝ossil record鈥� of potentially thousands of copies in the genome.

鈥淪o, the vast majority of these transposons are junk DNA, but not all of them. We thought that some of them must be important and must have shaped our evolution and biology.鈥�

A classic example of this is a set of genes called RAG1 and RAG2, which are responsible for shuffling human DNA to generate the virtually infinite variation in antibodies for adaptive immune response. Researchers have learned that these proteins originated from what was once a parasite 鈥渁nd our evolutionary ancestors were able to co-opt these proteins for an immune function,鈥� Chuong says. 鈥淭ransposons are a pivotal source of new genetic material and are increasingly appreciated to be important for adaptation and change in DNA.鈥�

Understanding immune response

Chuong鈥檚 research on transposons鈥� role in the immune system has looked at how they can regulate immune signaling and how they affect the communication system cells use to coordinate immune response.

鈥淲hen you get infected by a virus, immune cells detect that and release many cytokines, which are signaling proteins that help control inflammation; one of the most important of these is interferon,鈥� Chuong says. 鈥淥ther cells will detect interferon using a receptor on the outside of the cell, which causes the activation of immune genes.

鈥淏ut these are not genes that you want on all the time; that鈥檚 what would lead to autoimmunity. So, when a cell is stimulated with interferon, several hundred genes with antiviral and inflammatory functions become activated.鈥�

Activating interferon activates transcription factors, which are proteins that modulate how a cell translates DNA to RNA. They travel into the cell鈥檚 nucleus and trigger gene expression, or the process by which instructions in DNA are turned into a functional product like protein.

鈥淭he work that this award recognizes shows that a lot of these regulatory elements, you can think of them as switches or knobs,鈥� Chuong says. 鈥淭hey鈥檙e not coding DNA, but often are around or upstream of a gene. We鈥檝e found that these non-coding regulatory elements that control immune gene expression are themselves derived from transposons.鈥�

This research has potential implications for understanding and treating many diseases, including cancer. Chuong and his colleagues have found that some transposons that are usually inactive in healthy cells become reactivated in tumor cells. Future research may delve into what that means for making the immune system more susceptible to therapy.

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