Navigation Links
More accurate, powerful genetic analysis tool opens new gene-regulation realms

SALT LAKE CITYResearchers from Huntsman Cancer Institute (HCI) at the University of Utah have developed a novel and powerful technique to identify the targets for a group of enzymes called RNA cytosine methyltransferases (RMTs) in human RNA. They applied their technique to a particular RMT, NSUN2, which has been implicated in mental retardation and cancers in humans, finding and validating many previously unknown RMT targetsan indication of the technique's power. The research results were published online in the journal Nature Biotechnology on April 21.

"Although RMTs have been known for many years, virtually nothing is known about the majority of these enzymes in humans," said Bradley R. Cairns, co-author of the study and Senior Director of Basic Science at HCI. "This new technique will now allow the very rapid identification of the direct target RNAs for each human RMT, and we are excited about conducting that work."

Within all living cells, RNA acts as a critical intermediate in transmitting genetic information from DNARNA is made from DNA and then used to encode proteins called enzymes that control cell functions. A process called cytosine methylation attaches methyl molecules to cytosine bases in DNA and RNA molecules. RMTs act as catalysts to allow methylation at particular locations in RNA molecules. Methylation can regulate the flow of genetic information (from RNA to protein production) in cells, and it can change the way RNA interacts with proteins.

RNA methylation is currently poorly understood, partly because of limitations in the technique currently used to identify which RNA molecules and cytosine bases are RMT targets. As each cell contains thousands of different types of RNA molecules, often with only a small percentage being targets for a specific RMT, the first step in a study of RNA methylation is to sort out and concentrate the precise target RNA molecules for a particular RMT, in a process called enrichment.

The work involved a novel enrichment method, which applied a special "chemical cross-linker" to physically join the RMT to an RNA that it is trying to methylate, said Vahid Khoddami, the study's co-author and a member of the Cairns Lab. "Our new technique takes advantage of the mechanism of the enzyme. The drug/crosslinker we used looks like cytosine, so it is incorporated in place of the cytosine in the RNA. The RMT tries to methylate this drug thinking it is a normal target cytosinebut instead becomes crosslinked to the RNA, defining the precise location of the intended methylation. As our reaction-based method requires that the enzyme both bind the RNA and commit to the act of methylation, it greatly increases our identification of true positives," said Khoddami.

"This technique gives us 200-fold enrichment, when two-fold enrichment has been considered a great result in the past," said Khoddami. "In fact, for some RNA types, the enrichment is more than 700-fold."

After the enrichment process, high-throughput gene sequencing is used to analyze the RNA samples obtained.

"Our enrichment results were fantastic by themselves, but in the sequencing process we made another important discovery," Khoddami said. "We found that after sequencing, the target cytosine in the modified RNA instead appeared as an alternative molecule, guanosine, more than 50% of the time. After sequencing, you can look for these cytosine to guanosine transversions and know you have the precise targetin a single experiment."

According to Khoddami, ten cytosine RMTs are known in humans, and only two of them have been partially characterized. "None of the other eight have been studied in the laboratory," he explained, "although some of them have been shown to have connections to cancer, infertility, and particular genetic disorders in humans.

"These diseases have been puzzling because previously we did not have the tools to analyze the RNA. Now we have beautiful tools," said Khoddami.


Contact: Linda Aagard
University of Utah Health Sciences

Related medicine news :

1. 2 new vitamin D blood tests are often highly inaccurate, researchers say
2. Websites Touting Designer Vagina Surgeries Often Inaccurate, Study Finds
3. Florida Social Security Disability Attorney Larry Disparti Says Sequester Cuts Make Filing Accurate, Complete Claims Crucial
4. Moving 3D computer model of key human protein is powerful new tool in fight against cancer
5. Grb2 holds powerful molecular signaling pathway in check
6. Scripps Research scientists devise powerful new method for finding therapeutic antibodies
7. Epigenetics emerges powerfully as a clinical tool
8. Researchers reveal underlying mechanism of powerful chemotherapy for prostate cancer treatment
9. Dietary glucose affects the levels of a powerful oncogene in mice
10. New Online Resource Acts As Powerful Tool in the Battle against Cancer
11. NATural DISasters Now Has an Exclusive and Powerful Tool for December 21st, and All Other Future Doomsday Dates
Post Your Comments:
(Date:11/25/2015)... ... November 25, 2015 , ... On November 10, 2015, Bohrer Brady, ... of Connecticut on behalf of a home health care worker who provided companionship services ... home health care workers employed by Humana, Inc., Humana at Home, Inc., and SeniorBridge ...
(Date:11/25/2015)... Canadian, OK (PRWEB) , ... November 25, 2015 , ... ... and International training center for the Narconon network, announced the release of a new ... Since 1966 the Narconon organization has been working with drug- and alcohol-addicted individuals with ...
(Date:11/25/2015)... , ... November 25, 2015 , ... ... double board certified facial plastic surgeon specializing in both surgical and non-surgical treatments, ... The Skin Spa at Hobgood Facial Plastic Surgery. , Highly trained and ...
(Date:11/25/2015)... ... ... Today, Mothers Against Drunk Driving (MADD) learned that the number ... first time since 2011. In 2014, there were 9,967 fatalities involving an alcohol impaired ... Highway Traffic Safety Administration (NHTSA), 32,675 people were killed in traffic crashes in 2014. ...
(Date:11/25/2015)... ... ... An unlikely combination of recycled plastic shopping bags in ... to have a more dignified and comfortable night’s sleep. , Residents of Friendship ... bags into sleeping mats for the homeless. The project, according to Jeannette ...
Breaking Medicine News(10 mins):
(Date:11/25/2015)... - Will Also Offer Point -of- ... --> - Will Also Offer Point ... --> - Will Also Offer ... (CME) Elsevier , a world-leading provider of ... diagnostic imaging textbooks and decision support tools, as well as prominent ...
(Date:11/24/2015)... , November 25, 2015 ... due to repeated failure of IVF cycles. After failure ... was totally dejected and had lost all hopes that she would be able ... Indian miracle child conceived after failure of over 15 ... abroad (UK) before they decided to take one last attempt with ...
(Date:11/24/2015)... Nov. 24, 2015  Array BioPharma Inc. (Nasdaq: ... Executive Officer, Ron Squarer , will present ... New York.  The public is welcome to participate ... Array BioPharma website.Event:Piper Jaffray Annual Healthcare ConferencePresenter:  , ... 2, 2015Time:1:30 p.m. Eastern Time Webcast: ...
Breaking Medicine Technology: