Corporate Banner
Satellite Banner
Scientific Community
Become a Member | Sign in
Home>News>This Article

Charting the RNA Epigenome

Published: Monday, December 16, 2013
Last Updated: Monday, December 16, 2013
Bookmark and Share
In science, sometimes you need to dive deep to see the big picture.

Scientists at the Broad Institute have demonstrated this time and again, enabling biological discoveries by generating dense maps, such as the survey of thousands of epigenetic marks on DNA across the human genome conducted as part of the ENCODE project.

A team led by Broad researchers has recently created the first high-resolution map of another epigenetic landscape – the RNA epigenome, also known as the “epitranscriptome.” The work appears in the December 5 issue of Cell.

It’s been known since the 1970s that RNA, like DNA, can be tagged with methyl groups, in one kind of epigenetic modification. When DNA or chromatin is methylated, it can alter gene activity by making genes more or less open to being transcribed. The function of RNA methylation, however, has remained a mystery since the discovery of this phenomenon decades ago. A detailed map of epigenetic marks on mRNA across the transcriptome would allow scientists to start navigating the epitranscriptome and begin uncovering its functional role.

One reason RNA methylation is so elusive is that RNA can be tricky to work with. “When working with RNA, we often try to turn it into DNA as soon as possible, because DNA is stable and RNA is not,” said Schraga Schwartz, first author on the new study and a postdoctoral researcher in the laboratories of Broad core faculty members Eric Lander and Aviv Regev, a senior author. “But when studying epigenetic modifications of RNA, once you’ve turned it into DNA, it’s too late. The modifications are no longer going to be there. Whatever you do has to be done at the RNA level.”

Decades ago, scientists pioneered methods of using antibodies to capture modified fragments of the genetic material, but once the fragments were isolated, they had difficulty identifying them. Only with the latest advances in RNA sequencing – and more recently, methods to sequence very small amounts of RNA – could scientists begin to make real headway in the study of the epitranscriptome.

“Until recently, we just knew there was a lot of RNA methylation going on,” said Schwartz. “But nobody knew where.” He explained that better methods to map the modification of messenger RNA across the transcriptome are a first step to uncovering the modifications’ functional roles. “Where is this happening? That’s pretty much an elementary question before starting to address function.”

Before joining the Broad two years ago, Schwartz was part of a research team in Israel that developed a method to study RNA methylation by incorporating RNA sequencing.

At the Broad, Schwartz together with research associate Maxwell Mumbach further optimized the technique in several ways: by reducing the RNA fragment size used in sequencing, which increased the resolution of their map, and reducing the necessary amount of starting material. The team then joined forces with Sudeep Agarwala and Gerald Fink of the Whitehead Institute to map methylations in yeast cells, which experience peaks of RNA modification during meiosis, giving the scientists a dynamic system to study. “In yeast cells, we can really follow methylation as it comes and goes,” said Schwartz. Using yeast cells, the team was also able to shut down the enzyme that adds methyl groups to RNA, allowing them to eliminate many false positive sites.

These advances produced a high-resolution map of more than 1,300 sites of RNA methylation across the yeast transcriptome, down to the single nucleotide. The researchers also characterized the role of three proteins that make up the methylation machinery, shedding light on how these proteins are specifically regulated during meiosis. In addition, they identified a novel protein that binds specifically to methylated RNA. Future studies of these proteins should yield clues about the role of RNA methylations in the cell.

The precise regulation of methylation levels during meiosis suggests an important, still unknown, functional role for RNA methylation. Schwartz, Regev, and their fellow scientists are now pursuing studies to uncover the function of these epitranscriptomic changes, by perturbing those sites in both yeast and mammalian cells. “Our hope is that yeast can serve as a model organism for uncovering function and that a lot of this information will be applicable to humans, given the large extent of conservation that we find,” said Schwartz.

Results of this work may yield insights into disease mechanisms. For example, the top gene associated with obesity, FTO, is an enzyme involved in RNA methylation and, for this reason, obesity researchers are very interested in understanding more about the epitranscriptome.

With this new high-resolution map in hand, scientists can begin exploring the landscape of the RNA epitranscriptome. The work illustrates the importance of mapping in biological study. “You cannot navigate without a map,” explained Schwartz. “One of the most informative things one could do to discover the function of RNA methylation is to perturb specific sites, but that’s only possible once you know where the sites are.”

The field of epitranscriptomics is still relatively new, since techniques that make it feasible only arose in the last couple of years, explains Schwartz. “It’s fascinating for me to follow a field from its infancy and see how knowledge gradually accumulates over time through the joint work of an entire community.”

Further Information

Join For Free

Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 3,500+ scientific posters on ePosters
  • More than 5,100+ scientific videos on LabTube
  • 35 community eNewsletters

Sign In

Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Nanosensors Could Determine Tumours’ Ability to Remodel Tissue
Researchers design nanosensors that can profile tumours, focusing on protease levels.
Thursday, September 29, 2016
High-Capacity Nanoparticles
New type of nanoparticle can now have three or more drugs packaged within it, allowing for customised cancer therapy.
Thursday, September 15, 2016
Delivering Beneficial Bacteria
Method that transports microbes through the stomach to the intestine may benefit human health.
Thursday, September 15, 2016
Linking RNA Structure and Function
Biologists have deciphered a lncRNA structure and used the information to investigate its cellular protein interactions.
Friday, September 09, 2016
Triple-Action Therapy Patch Shows Promise
Patch that delivers drug, gene, and light-based therapy to tumor sites shows promising results in mice.
Wednesday, July 27, 2016
New Device can Study Electric Field Cancer Therapy
Microfluidic device allows study of electric field cancer therapy through low-intensity fields, preventing malignant cells spreading.
Friday, July 08, 2016
Long-Term Drug Release
New tablet attaches to the lining of the GI tract, resists being pulled away.
Thursday, April 07, 2016
Cancer Cells Remodel Environments Before Spreading
Researchers at MIT have found that the cancer cells remodel their environment to make it easier to reach nearby blood vessels.
Wednesday, March 16, 2016
Paving the Way for Metastasis
Cancer cells remodel their environment to make it easier to reach nearby blood vessels.
Tuesday, March 15, 2016
Curing Disease by Repairing Faulty Genes
New delivery method boosts efficiency of CRISPR genome-editing system.
Wednesday, February 03, 2016
No More Insulin Injections?
Encapsulated pancreatic cells offer possible new diabetes treatment.
Tuesday, January 26, 2016
Engineering Foe into Friend
Bose Grant awardee Jacquin Niles aims to repurpose the malaria parasite for drug delivery.
Monday, January 25, 2016
Supply Chain
Chemists discover how a single enzyme maintains a cell’s pool of DNA building blocks.
Wednesday, January 13, 2016
How Cancer Cells Spread
Study offers new targets for drugs that may prevent cancer from spreading.
Thursday, December 17, 2015
Delivering microRNAs for Cancer Treatment
Scientists exploit gene therapy to shrink tumors in mice with an aggressive form of breast cancer.
Wednesday, December 09, 2015
Scientific News
Integrated Omics Analysis
Studying multi-omics promises to give a more holistic picture of the organism and its place in its ecosystem, however despite the complexities involved those within the field are optimistic.
Unravelling the Role of Key Genes and DNA Methylation in Blood Cell Malignancies
Researchers from the University of Nebraska Medical Center have demonstrated the role of Dnmt3a in safeguarding normal haematopoiesis.
Agilent Presents Early Career Professor Award to Dr. Roeland Verhaak
JAX professor recognized for the development and implementation of workflows for the analysis of big-data from transcriptomics to next generation sequencing approaches.
New Mechanism of Plant RNA Degradation Identified
Researchers have identified a novel mechanism by which RNA is degraded.
Enlisting Insects to Protect Agriculture
New program aims for insect delivery of protective genes to modify mature plants within a single growing season.
Ovarian Cancer Insight
Study showed tumours release cytokines to attract macrophages, which secrete growth factors that in turn promote tumour growth.
Less Frequent Cervical Cancer Screening
HPV-vaccinated women may only need one screening every 5 to 10 years with screening starting later in life.
Questioning the Safety of Selenium to Combat Cancer
Research indicates the need for change in practice as selenium supplements cannot be recommended for preventing colorectal cancer.
Supercomputers Could Improve Cancer Diagnostics
Researchers push the boundaries of cancer research through high-performance computing to map the human immunone.
Transgenomic, Precipio Diagnostics Merger
Merger will creates a robust diagnostic platform focused on improving accuracy of cancer diagnoses.

SELECTBIO Market Reports
Go to LabTube
Go to eposters
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
3,500+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
5,100+ scientific videos