Top Stories - RNA Biology

Chao-Shun Yang, graduate student in Dr. Tariq Rana's lab and first author of the study
An easier (and safer) route to...

Could there be a safer and more predictable way to reprogram adult skin cells into induced...

Zhonghan Li, graduate student in the Rana lab, studies microRNA and iPS cells.
New recipe for iPS cells

Generating iPS cells can be an arduous task. Reprogramming differentiated adult cells into iPS cells...

Dr. Tariq Rana
Hibernating herpes viruses

Herpes viruses are good at hiding. They infect human cells and lay dormant there until replication...

Melanoma cells, with nuclei in blue and SPRY4-IT1 in green. (Image courtesy of the Perera lab)
One cell’s junk is...

In a paper published May 10 in the journal Cancer Research, Dr. Ranjan Perera and colleagues show...

It’s a trap! New laboratory technique captures microRNA targets

Full Article

Human cells are thought to produce thousands of different microRNAs (miRNAs)—small pieces of genetic material that help determine which genes are turned on or off at a given time. miRNAs are an important part of normal cellular function, but they can also contribute to human disease—some are elevated in certain tumors, for example, where they promote cell survival. But to better understand how miRNAs influence health and disease, researchers first need to know which miRNAs are acting upon which genes—a big challenge considering their sheer number and the fact that each single miRNA can regulate hundreds of target genes. Enter miR-TRAP, a new easy-to-use method to directly identify miRNA targets in cells. This technique, developed by Tariq Rana, Ph.D., professor and program director at Sanford-Burnham, and his team, was first revealed in a paper published May 8 by the journal Angewandte Chemie International Edition.

“This method could be widely used to discover miRNA targets in any number of disease models, under physiological conditions,” Rana said. “miR-TRAP will help bridge a gap in the RNA field, allowing researchers to better understand diseases like cancer and target their genetic underpinnings to develop new diagnostics and therapeutics. This will become especially important as new high-throughput RNA sequencing technologies increase the numbers of known miRNAs and their targets.”

Sisters in science

Full Article

In late 2007, the Sanford Children’s Health Research Center was established at Sanford-Burnham’s La Jolla campus with a $20 million gift from South Dakota philanthropist T. Denny Sanford through Sanford Health. The gift was the foundation for a long-term partnership between Sanford Health, a large healthcare system based in South Dakota, and Sanford-Burnham. In addition to the center in La Jolla, in 2009 Sanford Health created a sister Children’s Health Research Center in Sioux Falls.

On October 27-28, researchers from both research centers gathered at Sanford-Burnham’s La Jolla campus to share new research directions and stimulate further collaboration at the fourth annual Sanford Children’s Health Research Center Scientific Symposium. Attendees heard overviews from the leaders of both Sanford-Burnham and Sanford Health and learned about Sanford Health’s new BioBank, a repository for patient samples that will help drive personalized medicine and provide fodder for population genomics studies. More than a dozen scientists presented their ongoing studies of embryonic development, type 1 diabetes, brain tumors, lung injury in newborns, and rare inherited conditions such as Batten disease. Hot topics also included stem cells and RNA biology.

An easier (and safer) route to stem cell therapies

Full Article

Many research labs around the world are focused on finding the most effective ways to reprogram an adult cell (a skin cell, for example) into induced pluripotent stem cells (iPSCs)—that is, cells that have the ability to develop into other tissues in the body. These cells not only offer researchers powerful tools to study a particular patient’s individual disease, but they have the potential to therapeutically replace diseased or damaged tissue in the patient from whom the cells originated.

Most experiments to reprogram adult cells employ viruses as vehicles to carry four particular genes—called reprogramming factors—into the nucleus of a cell. But genetic engineering carries its own risks, including the chance that these cells will continue replicating, eventually forming a tumor. What’s more, scientists are not exactly sure what the reprogramming factors do, on the molecular level, to promote the generation of iPSCs.

Could there be a safer and more predictable way to alter the expression of genes in cells, thereby reprogramming their DNA so they revert to their earlier, more malleable state?

A medical revolution

Full Article

A syndicated article that recently appeared in the Orlando Sentinel, the Los Angeles Times and other outlets described several revolutionary technologies that will change medicine in the coming decade. In particular, the piece highlighted how new genomic technologies can personalize treatment to individual patients; how robotic surgery will help surgeons perform complex procedures on people thousands of miles away; and how new classes of diagnostic tests will allow physicians to discover diseases earlier, when they are most treatable.The article included insights from Dr. Ranjan Perera, associate professor at Sanford-Burnham’s Lake Nona campus, and Dr. Jamey Marth, who directs the U.C. Santa Barbara–Sanford-Burnham Center for Nanomedicine. Dr. Marth is particularly excited about nanomedicine’s potential to enhance both diagnosis and treatment:

“Today’s scientists work at the molecular and atomic level with nanoparticles, to harness these biomachines that detect and bind to diseased cells. The nanoparticle then fuses with that sick cell and delivers its cargo — drugs or imaging agents.”

Read ‘Revolution is at hand’ for breakthroughs in medicine.

One cell’s junk is another’s treasure

Full Article

Scientists used to think RNA was mostly just a messenger molecule that carries protein-making instructions from a cell’s nucleus to the cytoplasm. But scientists now estimate that 97 percent of human RNA doesn’t actually code for proteins at all. A flurry of research in the past decade has revealed that some types of non-coding RNAs switch genes on and off and influence protein function. The best studied non-coding RNAs are the microRNAs, but Dr. Ranjan Perera and his collaborators are discovering that levels of a relatively understudied group of RNAs – long, non-coding RNA (lncRNA) – are altered in human melanoma. Their study, published online May 10 by the journal Cancer Research, shows that one lncRNA called SPRY4-IT1is elevated in melanoma cells, where it promotes cellular survival and invasion.

“Non-coding RNA used to be considered cellular junk. But we and others have been asking the question – if it doesn’t code for proteins, what does it do in the cell?” said Dr. Perera, associate professor at Sanford-Burnham’s Lake Nona campus in Orlando, Fla. “We’re especially interested in determining what roles microRNAs and lncRNAs play in the genesis and development of human melanomas.”

Melanoma is one of the rarest forms of skin cancer, but it is also the most deadly.

New recipe for iPS cells

Full Article

Stem cells are ideal tools to understand disease and develop new treatments because they can self-renew (generate more cells in a dish) and differentiate (become a wide variety of cell types). They can be differentiated into heart muscle cells, for example, which could then be used to replace damaged heart tissue. Where do scientists get stem cells? In the early days of stem cell research, investigators could isolate stem cells from pathological specimens of the brain or bone marrow. More recently, they have figured out how to make a special kind of stem cell called an induced pluripotent stem cell (iPS cell) from almost any type of adult cell, such as a skin cell. Researchers can then use iPS cells to study human development or to create “disease in a dish”, a technique that allows them to model an individual patient’s specific disease and screen for personalized treatments.

But generating iPS cells can be an arduous task. Reprogramming differentiated adult cells into iPS cells requires so many steps and so much time that the efficiency rate is very low – you might end up with only a few iPS cells even if you started with a million skin cells. So a team set out to improve the process. In a paper published February 1, 2011 in The EMBO Journal, they uncovered microRNAs (miRNAs) that are important during reprogramming and exploited them to make the transition from skin cell to iPS cell more efficient.

“We identified several molecular barriers early in the reprogramming process and figured out how to remove them using miRNA,” said Dr. Tariq Rana, senior author of the study. “This is significant because it will enhance our ability to use iPS cells to model diseases in the laboratory and search for new therapies.”

Reining in melanoma with MicroRNA

Full Article

Skin cancer is the most common cancer in the United States. Melanoma is one of the rarest forms of skin cancer, but it is also the most deadly. At Sanford-Burnham’s Lake Nona campus, Dr. Ranjan Perera’s lab is studying what causes melanocytes (pigment-producing skin cells) to divide abnormally, ultimately forming melanoma. In a study published today in the journal PLoS ONE, a team led by Dr. Perera and post-doctoral researcher Dr. Joseph Mazar show that melanocyte growth and the cancer’s ability to invade other tissue is at least partially controlled by abnormal expression of microRNAs (miRNAs) – small strands of genetic material that may play a major role in numerous diseases by interfering with proteinproduction.“We’ve identified one specific miRNA, called miR-211, that could be used not only as a novel diagnostic marker for early melanoma detection, but also as a therapeutic target,” explains Dr. Perera, associate professor in Sanford-Burnham’s RNA Biology Program and senior author of the study.

Hibernating herpes viruses

Full Article

Herpes viruses are good at hiding. They infect human cells and lay dormant there until replication is activated by stress or some other environmental factor. One type, Kaposi’s sarcoma-associated herpesvirus (KSHV), is one of only a few viruses known to cause cancer.

In a study that appeared online September 17 in the journal EMBO Reports, Sanford-Burnham’s Dr. Tariq Rana and colleagues found that KSHV stays quiet by expressing certain microRNAs (miRNAs), small strands of genetic material that interfere with protein production.

“KSHV dormancy is believed to be essential for tumor formation, yet some forms of cancers caused by the virus have also been linked to viral reactivation,” explains Dr. Rana, professor and director of Sanford-Burnham’s RNA Biology Program. “This study helps us better understand the KSHV life cycle, thus providing new insight into how the virus causes cancer in some populations.”

RNApalooza

Full Article

Until recently, RNA had been thought of simply as a messenger, transferring encoded information from our DNA to ribosomes, which produce proteins. But in the past 10 years, scientists have found that specific types of RNA, called microRNA and RNAi, play a significant role in controlling which genes are turned on or off—processes that could have a profound impact on human health.

On May 7, scientists from around the country came to Sanford-Burnham’s 32nd Annual Scientific Symposium to discuss the implications of these small RNAs and how we can use them to fight disease.

It’s a small RNA world

Full Article

We’re oversimplifying a little, but our genetic code works like this: DNA codes for messenger RNA (mRNA); mRNA takes that coded message out of the nucleus; tiny machines called ribosomes read the message in the mRNA and produce proteins; proteins do most of the work in the cell. However, there is another player in this pathway that has only come to light relatively recently—microRNAs(miRNAs).