Method developed by biomedical scientists could help in treatment of several diseases

February 17, 2017
Sika Zheng is an assistant professor of biomedical sciences in the School of Medicine at UC Riverside. Credit: I. Pittalwala, UC Riverside.

In cells, DNA is first converted to RNA, and RNA is next converted to proteins—a complicated process involving several other steps. Nonsense-mediated RNA decay (NMD) is a processing pathway in cells that, like a broom, cleans up erroneous RNA to prevent its productive conversion into an aberrant protein, which could lead to disease.

In some diseases, like amyotrophic lateral sclerosis (ALS, also called Lou Gehrig's disease), excessive junk RNA is produced, possibly contributing to the disease. In such instances, more NMD is useful to get rid of the junk RNA.

In other diseases, such as muscular dystrophy and cystic fibrosis, a decrease in NMD is a better option. In these diseases, the NMD pathway eliminates the RNA, resulting in a complete loss of the gene function. But a defective RNA may translate to a semi-functional protein, which is better than no RNA for protein formation in cells. And so, a tuned-down NMD is more useful.

Sika Zheng, an assistant professor of biomedical sciences in the School of Medicine at the University of California, Riverside, and colleagues now report in the journal RNA (volume 23, no.3, March 2017 issue) that they have come up with a in the lab that detects NMD efficiency inside the cell.

"Our method can screen a host of chemicals and allows us to identify molecules that regulate this efficiency," Zheng said. "We have already identified thapsigargin as a molecule that indirectly and robustly inhibits NMD."

The new method works by harnessing some normal targets of NMD and turning them into "reporters" of NMD activity. The method relies on the knowledge that NMD is more than a quality-control mechanism; it can also determine the level of some naturally occurring RNA. The lower the abundance of these natural NMD in a cell, the stronger the NMD activity, and vice versa.

Zheng explained that in the past, measuring NMD efficiency was a cumbersome process and could be performed only on cell cultures, not directly on tissues.

"Our method is far easier and more sensitive, and for the first time can make measurements in all kinds of samples," Zheng said. "This is essential for drug screening. We are going to screen a larger library of chemicals to identify molecules that either boost or weaken NMD, which should help develop better and more targeted drugs for treating ALS, and cystic fibrosis."

Explore further: Researchers uncover a new mechanistic understanding of potential treatment for genetic disorders

Related Stories

Researchers uncover a new mechanistic understanding of potential treatment for genetic disorders

October 4, 2016
A study published today by scientists at University of Massachusetts Medical School and the University of Alabama at Birmingham provides insight into the mechanism of action of the drug ataluren, which is showing promise ...

New target may slow disease progression in Duchenne muscular dystrophy

September 12, 2016
Duchenne muscular dystrophy is a chronic disease causing severe muscle degeneration that is ultimately fatal. As the disease progresses, muscle precursor cells lose the ability to create new musclar tissue, leading to faster ...

New knowledge about serious muscle disease

October 31, 2013
About 3,000 people in Denmark suffer from one of the serious muscle-related diseases that come under the heading of muscular dystrophy. Some patients diagnosed with muscular dystrophy die shortly after birth, others become ...

Recommended for you

'Human chronobiome' study informs timing of drug delivery, precision medicine approaches

December 13, 2017
Symptoms and efficacy of medications—and indeed, many aspects of the human body itself—vary by time of day. Physicians tell patients to take their statins at bedtime because the related liver enzymes are more active during ...

Estrogen discovery could shed new light on fertility problems

December 12, 2017
Estrogen produced in the brain is necessary for ovulation in monkeys, according to researchers at the University of Wisconsin-Madison who have upended the traditional understanding of the hormonal cascade that leads to release ...

Time of day affects severity of autoimmune disease

December 12, 2017
Insights into how the body clock and time of day influence immune responses are revealed today in a study published in leading international journal Nature Communications. Understanding the effect of the interplay between ...

3-D printed microfibers could provide structure for artificially grown body parts

December 12, 2017
Much as a frame provides structural support for a house and the chassis provides strength and shape for a car, a team of Penn State engineers believe they have a way to create the structural framework for growing living tissue ...

Team identifies DNA element that may cause rare movement disorder

December 11, 2017
A team of Massachusetts General Hospital (MGH) researchers has identified a specific genetic change that may be the cause of a rare but severe neurological disorder called X-linked dystonia parkinsonism (XDP). Occurring only ...

Protein Daple coordinates single-cell and organ-wide directionality in the inner ear

December 11, 2017
Humans inherited the capacity to hear sounds thanks to structures that evolved millions of years ago. Sensory "hair cells" in the inner ear have the amazing ability to convert sound waves into electrical signals and transmit ...

0 comments

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.