Study reveals a role for jumping genes during times of stress

December 23, 2019

BOSTON - Only percent of human DNA codes for proteins, and approximately half of the rest of the genome is made up of what used to be called "junk" sequences that can copy themselves into RNA or DNA and jump from one location to another. Previous research led by investigators at Massachusetts General Hospital (MGH) had revealed a critical role for one of these jumping genes during times of stress. In new research published by the same group in the Proceedings of the National Academy of Sciences, the investigators report a surprising new property of this jumping RNA.

The sequences that jump from place to place in the genome are more formally known as transposable elements, and their role in health and disease is not fully understood. But it has long been suspected that they are more than just parasitic elements without good function. In their original study, Jeannie Lee, MD, PhD, an investigator in the Department of Molecular Biology at MGH, and her colleagues found that one of these transposable elements--a very abundant, short interspersed nuclear element (SINE) called B2 in mice (ALU in humans)--makes an RNA that is cut when together with a protein called EZH2. However, at the time, they did not know how the RNA is cut. Researchers now make the striking discovery that B2 and ALU cut themselves.

Until four decades ago, it was thought that only proteins can make enzymes and that only enzymes can cut nucleic acids, the building blocks of DNA and RNA. But in 1982, researchers showed that RNA can function as enzymes as well--and these RNAs are called ribozymes -- a discovery that led to the Nobel Prize in Chemistry in 1989. Today, 15 classes of ribozymes have been described, but they are mostly observed in bacteria and viruses. Very few are known in mammals such as humans, and their functions are mostly unclear.

Because B2 and ALU are so abundant in our cells, the Lee group's discovery puts a new twist to the ribozyme story. "B2 and ALU are present in hundreds of thousands of copies in our DNA and they become massively expressed during stress. This is a mind-boggling amount of ribozyme activity," said Lee. The team found that B2 and ALU are normally silent, but when subjected to heat or other forms of stress, they become activated. Also, their RNA-cutting activity is enhanced by an interaction with the EZH2 protein.

Lee noted that cells are continually challenged by stress, and a swift response can mean the difference between life and death. "Hinging the induction of stress-related genes to self-cutting RNAs seems highly adaptive," she said. "No new synthesis of gene products would be required and the critical event would instead be the recruitment of a protein factor, EZH2, that already exists inside cells and stands ready to be mobilized."

The findings may have important clinical implications for helping the body to respond to stress, such as during the development of infections, cancer or autoimmune disease.
About the Massachusetts General Hospital

Massachusetts General Hospital, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH Research Institute conducts the largest hospital-based research program in the nation, with an annual research budget of more than $1 billion and comprises more than 8,500 researchers working across more than 30 institutes, centers and departments. In August 2019 the MGH was once again named #2 in the nation by U.S. News & World Report in its list of "America's Best Hospitals."

Massachusetts General Hospital

Related Stress Articles from Brightsurf:

Stress-free gel
Researchers at The University of Tokyo studied a new mechanism of gelation using colloidal particles.

Early life stress is associated with youth-onset depression for some types of stress but not others
Examining the association between eight different types of early life stress (ELS) and youth-onset depression, a study in JAACAP, published by Elsevier, reports that individuals exposed to ELS were more likely to develop a major depressive disorder (MDD) in childhood or adolescence than individuals who had not been exposed to ELS.

Red light for stress
Researchers from the Institute of Industrial Science at The University of Tokyo have created a biphasic luminescent material that changes color when exposed to mechanical stress.

How do our cells respond to stress?
Molecular biologists reverse-engineer a complex cellular structure that is associated with neurodegenerative diseases such as ALS

How stress remodels the brain
Stress restructures the brain by halting the production of crucial ion channel proteins, according to research in mice recently published in JNeurosci.

Why stress doesn't always cause depression
Rats susceptible to anhedonia, a core symptom of depression, possess more serotonin neurons after being exposed to chronic stress, but the effect can be reversed through amygdala activation, according to new research in JNeurosci.

How plants handle stress
Plants get stressed too. Drought or too much salt disrupt their physiology.

Stress in the powerhouse of the cell
University of Freiburg researchers discover a new principle -- how cells protect themselves from mitochondrial defects.

Measuring stress around cells
Tissues and organs in the human body are shaped through forces generated by cells, that push and pull, to ''sculpt'' biological structures.

Cellular stress at the movies
For the first time, biological imaging experts have used a custom fluorescence microscope and a novel antibody tagging tool to watch living cells undergoing stress.

Read More: Stress News and Stress Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to