Newfound mechanism may yield ways to counter mistaken immune attack on body

November 27, 2018, NYU Langone Health
Credit: CC0 Public Domain

A newfound genetic regulatory mechanism may shape the immune system's ability to fight viral infections, and play a key role in autoimmune diseases that occur when immune cells attack bodily tissues.

A new study led by researchers at NYU School of Medicine found that chemical changes to key spots on messenger RNA (mRNA) - the genetic material that passes on DNA instructions—control the production of a protein called interferon beta, which causes inflammation and activates to destroy viral particles.

Published online in Genes and Development on Nov. 27, the study shows how a pair of enzymes control production of interferon beta by determining whether or not a (one carbon and three hydrogens) is attached to an adenosine, one of the chemical "letters" in the mRNA code that guides the protein building process.

Methylation at a specific position on adenosine called N-6 by an enzyme called m6A methyltransferase is counter-balanced by the enzyme ALKBH5, which erases this methylation "mark." The researchers found that this writer/eraser pair, in partnership with other proteins, influenced how much interferon beta mRNA was produced in response to infection with human cytomegalovirus (HCMV), a common infection that begins by injecting its DNA into human cells.

The found that interfering with the enzyme that installs the methylation marks at N-6 resulted in greater interferon production, while shutting down the that removes groups there reduced interferon production.

Importantly, say the authors, the proteins that edit RNA methylation marks were also found to control how much interferon beta was produced by human cells not infected by HMCV, when they sensed that human DNA had escaped from the cell nucleus or mitochondria where it belongs. This can happen when DNA is damaged by chemicals or radiation, or with changes to the structure of the nucleus or mitochondria as cells age.

As misplaced DNA is a known trigger of inflammation in autoimmune and inflammatory diseases, not to mention the aging process, the study mechanisms may represent a newfound treatment approach.

"Our study found that the cellular machinery that controls adenosine methylation on position N-6 plays a fundamental role shaping the immune response of human cells," says senior study author Ian Mohr, Ph.D., a professor in the Department of Microbiology at NYU Langone Health.

"Many diseases, such as lupus, are associated with excess interferon production related to the sensing of misplaced DNA, and our new findings suggest that interfering with enzymes that chemically modify mRNA may represent new ways to treat these conditions," says Mohr.

Experiments also showed that cellular writers and erasers of the methylation marks control the stability of mRNA by interacting with other carefully regulated mechanisms that influence how much mRNA is built (biogenesis) and how quickly it is broken down (mRNA decay).

Explore further: New role for protein could lead to novel treatments for cancer and vascular disease

Related Stories

New role for protein could lead to novel treatments for cancer and vascular disease

October 25, 2018
Researchers at York University have found a new role for a well-known protein in the body that may explain, in part, what goes wrong in certain cancers, as well as vascular and neurological disorders.

Zika virus infection alters human and viral RNA

October 20, 2016
Researchers at University of California San Diego School of Medicine have discovered that Zika virus infection leads to modifications of both viral and human genetic material. These modifications—chemical tags known as ...

Signal flare – how heart muscle cells protect themselves from viral invaders

September 29, 2017
The human heart is particularly vulnerable to viruses. That's because cardiac myocytes, the heart muscle cells that give your heart its ability to "beat," have one major weakness – they don't reproduce themselves to repair ...

Immune cells that create and sustain chronic inflammatory bowel disease identified

June 26, 2018
In preclinical experiments, Laurie Harrington, Ph.D., and colleagues at the University of Alabama at Birmingham have discovered a subset of immune cells that create and sustain chronic inflammatory bowel disease. These cells ...

New knowledge on how HIV beats the body's early immune response

September 14, 2017
In an important step towards eradicating HIV-associated viral reservoirs, researchers at Sydney's Westmead Institute for Medical Research have identified how the HIV virus hijacks the innate immune system to facilitate its ...

Recommended for you

HIV vaccine protects non-human primates from infection

December 14, 2018
For more than 20 years, scientists at Scripps Research have chipped away at the challenges of designing an HIV vaccine. Now new research, published in Immunity, shows that their experimental vaccine strategy works in non-human ...

RNA processing and antiviral immunity

December 14, 2018
The RIG-I like receptors (RLRs) are intracellular enzyme sentries that detect viral infection and initiate a first line of antiviral defense. The cellular molecules that activate RLRs in vivo are not clear.

The 'greying' of T cells: Scientists pinpoint metabolic pathway behind age-related immunity loss

December 13, 2018
The elderly suffer more serious complications from infections and benefit less from vaccination than the general population. Scientists have long known that a weakened immune system is to blame but the exact mechanisms behind ...

Scientists create most accurate tool yet developed to predict asthma in young children

December 13, 2018
Scientists at Cincinnati Children's Hospital Medical Center have created and tested a decision tool that appears to be the most accurate, non-invasive method yet developed to predict asthma in young children.

New genetic study could lead to better treatment of severe asthma

December 12, 2018
The largest-ever genetic study of people with moderate-to-severe asthma has revealed new insights into the underlying causes of the disease which could help improve its diagnosis and treatment.

Researchers discover unique immune cell likely drives chronic inflammation

December 11, 2018
For the first time, researchers have identified that an immune cell subset called gamma delta T cells that may be causing and/or perpetuating the systemic inflammation found in normal aging in the general geriatric population ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.