Discovery of new type of RNA could have implications for some congenital disorders

October 29, 2012 by Lisa Catanese, University of Connecticut

State funding of stem cell research at the UConn Health Center has led one research team to the discovery of a new type of RNA that could one day result in the successful treatment of devastating congenital disorders such as Prader-Willi syndrome.

Gordon Carmichael, professor in the Department of Genetics and Developmental Biology, together with his former Ph.D. student Ling-Ling Chen, who is now a professor, along with her students in Shanghai, used to look through the entire to search for new molecules. "We found RNAs that no one had ever found before," Carmichael says. "We found it using a unique mechanism that we had discovered. This RNA was missed because it didn't have the typical identifiers of other types of RNA."

The newly discovered sno-IncRNAs, described in an article published in the Oct. 26, 2012 issue of Molecular Cell, is located in a region of the human genome that is not expressed in patients with Prader-Willi syndrome (PWS) and Angelman syndrome (AS). "Every Prader-Willi patient in the world fails to express these RNAs," Carmichael explains. "We went on with our study and found out how we think they are working."

In a lab virtually next door to Carmichael's are researchers Marc Lalande and Stormy Chamberlain, whose team used state stem cell funds to create of PWS and AS. "We just stumbled on this discovery," Carmichael says of his work, "and it just so happens that two of the world's experts on these diseases are flanking us. It's now leading to collaborations between our labs and major new molecular insight."

"The goal of stem cell research is to improve , and at UConn we have a large portfolio of stem cell research projects," says Lalande, professor and chairman of Genetics and Developmental Biology. "Our labs have generated stem cells from the skin of Prader-Willi and Angelman patients. The new class of RNA discovered by Gordon Carmichael has significant importance in these two syndromes. So two very separate projects funded by the state initially, and now federally, have crossed paths and intersected to advance our knowledge of a complex human genetic disorder. That's remarkable."

The state committed to a 10-year, $100 million investment in stem cell research starting in 2006. The early results from that research jump-started funding from federal grants and other sources. The goal of the state's investment is to move Connecticut toward becoming a national and world leader in . This in turn could have huge economic benefits, such as start-up companies, as scientists learn how to repair or replace damaged or missing genetic to treat a wide variety of diseases.

Carmichael, whose research initially had focused on mouse viruses, moved to stem cells when he received one of the first state grants. "Stem cell grants have changed my world," he says. "This type of funding has changed how I do science. Now my expertise is in studying the underlying mechanism of disease." His research has resulted in more than a dozen major papers published worldwide, and grants flowing into the Health Center at a time of stiff competition for funds.

Prader-Willi syndrome is a congenital disease caused by missing paternal genes on part of chromosome 15. These genetic changes occur randomly; patients usually do not have a family history of the condition. Signs of PWS at birth include poor weight gain and failure to grow and thrive in early infancy. As PWS children grow, this reverses itself. In addition to having intellectual and behavioral disabilities, they develop an intense craving for food, often resulting in morbid obesity. These symptoms can in turn lead to diabetes and other serious health problems.

Angelman syndrome is a disorder that involves the same part of chromosome 15 as PWS and results from the lack of a functional copy of the UBE3A gene inherited from the mother. Infants often have feeding problems from birth and developmental delays by 12 months. Seizures usually begin between ages 2 and 3. Children will experience impaired speech, motor difficulties, hyperactivity, and balance and sleep disorders that continue into adulthood.

Research into these related disorders is encouraged and funded by the Foundation for Prader-Willi Syndrome, says Theresa Strong, chairwoman of the Foundation's scientific advisory board. "Because Prader-Willi is a rare disorder, patient advocacy groups are important in promoting research. Mouse models do not recapitulate disease very well. Stem cells allow the scientific community to study this disease in a way that they have never been able to study it before."

As the parent of an 18-year-old son with PWS, Strong says she yearns for an effective treatment, of which there currently are few. Most families live with locks on their cabinets and refrigerator. The chronic hunger of PWS patients lasts a lifetime.

"Failure to thrive when children are very young is replaced by an insatiable appetite," she says. "They are constantly hungry but don't need that many calories. It's a nightmare scenario where you have to restrict their environment, because food is all around us. They can't be independent because they can't control their appetite. It's a source of frustration all around."

Research into PWS could lead to life-changing results, says Strong, who is a scientist herself. "If not for the hunger issue, there's a lot that many of these kids could do. We could make a significant impact in their lives and their ability to contribute to society."

Explore further: Oxytocin promises hope in Prader-Willi syndrome

Related Stories

Oxytocin promises hope in Prader-Willi syndrome

June 24, 2011
Prader-Willi syndrome is a rare genetic disorder which affects one child in 25,000. Children born with this syndrome have a range of complex neurological and developmental problems which continue into adult life. These can ...

Recommended for you

More surprises about blood development—and a possible lead for making lymphocytes

January 22, 2018
Hematopoietic stem cells (HSCs) have long been regarded as the granddaddy of all blood cells. After we are born, these multipotent cells give rise to all our cell lineages: lymphoid, myeloid and erythroid cells. Hematologists ...

How metal scaffolds enhance the bone healing process

January 22, 2018
A new study shows how mechanically optimized constructs known as titanium-mesh scaffolds can optimize bone regeneration. The induction of bone regeneration is of importance when treating large bone defects. As demonstrated ...

Bioengineered soft microfibers improve T-cell production

January 18, 2018
T cells play a key role in the body's immune response against pathogens. As a new class of therapeutic approaches, T cells are being harnessed to fight cancer, promising more precise, longer-lasting mitigation than traditional, ...

Weight flux alters molecular profile, study finds

January 17, 2018
The human body undergoes dramatic changes during even short periods of weight gain and loss, according to a study led by researchers at the Stanford University School of Medicine.

Secrets of longevity protein revealed in new study

January 17, 2018
Named after the Greek goddess who spun the thread of life, Klotho proteins play an important role in the regulation of longevity and metabolism. In a recent Yale-led study, researchers revealed the three-dimensional structure ...

The HLF gene protects blood stem cells by maintaining them in a resting state

January 17, 2018
The HLF gene is necessary for maintaining blood stem cells in a resting state, which is crucial for ensuring normal blood production. This has been shown by a new research study from Lund University in Sweden published in ...


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.