New tool for breaking the epigenetic code

Feb 29, 2012 By Marcia Goodrich
This illustration shows the traditional view of RNA making proteins, left; how small RNA interferes with protein production, center; and how Tang's team interfered with the process by introducing a man-made gene to the mix. Credit: Guiliang Tang illustration

(PhysOrg.com) -- For the last dozen years, scientists have known that minuscule strings of genetic material called small RNA are critically important to our genetic makeup. But finding out what they do hasn’t been easy. Now a scientist from Michigan Technological University and his team have developed a way to turn off small RNAs and find out just how important they can be.

When it comes to inheritance, DNA is just the half of it. What we are is also driven by the epigenetic world of : the countless, twisting molecules that DNA churns out. RNA in turn transforms the amino acid soup in our cells into the proteins that are us—and every other plant and animal on the planet, for that matter.

There’s more than one kind of RNA, however. In addition to the long strings that make proteins, there are short, meddling snippets called small RNAs. Sometimes, they can attach to long RNA molecules and break them in two. That obviously has consequences for the organism, but exactly what role the thousands of different small RNAs play has been a puzzle.

Now, Guiliang Tang, an associate professor of biological sciences, has developed a way to put a single small RNA out of commission and observe what happens when it can’t do its job.

To do this, Tang and his team threw a wrench into a well-understood process that controls leaf symmetry and the tendency of plants to grow upright.

First they synthesized a sequence of DNA that would make a custom-designed type of small RNA, called a small tandem target mimic, or STTM (see Figure). Then they introduced their synthetic DNA in Arabidopsis, a plant often used in genetics research. Once in the Arabidopsis, the synthetic DNA began manufacturing many copies of the STTM.

Then all the little STTMs began locking onto strands of a specific type of RNA, right where the plant’s small RNA would normally have cut them in two. That blocked its action, so the long RNA strands remained intact.

When Guiliang Tang's research team knocked out a certain piece of small RNA, it caused Arabidopsis to grow shapelessly compared to a control plant, left. Credit: Guiliang Tang

Furthermore, the procedure prompted the cell to destroy all of its own small RNAs that would normally have cut the RNA. Together, those two mechanisms allowed the long RNA to make its protein unabated.

The results were dramatic. The control Arabidopsis plants grew upward on a central stem with regularly shaped leaves and stems. The mutant plants were smaller, tangled, and amorphous.

Their method isn’t limited to one small RNA involved in leaf symmetry in Arabidopsis.

“You can use this to study the function of any small RNA in the cell,” says Tang.

In an online commentary, Plant Cell senior features editor Nancy Eckardt called their method “a highly effective and versatile tool” for studying the functions of small RNA.

Now, Tang hopes to find out how and why this procedure causes cells to destroy small RNA. And his wife and fellow researcher Xiaoqing Tang, an assisant professor of biological sciences, plans to use this technology to better understand type 2 diabetes.

Their work is funded by the National Science Foundation and described in the article “Effective Small Destruction by the Expression of a Short Tandem Target Mimic in Arabidopsis,” published Feb. 16 online in the journal Plant Cell. The lead authors of the paper are students who worked with Tang: Jun Yan, now a postdoctoral researcher at Purdue University, and Yiyou Gu, now an undergraduate at Nanjing Agricultural University, in China. Other coauthors are Xiaoyun Jia, Wenjun Kang and  Shangjin Pan of the University of Kentucky and Xuemei Chen of the University of California at Riverside.

Explore further: Scientists call for investigation of mysterious cloud-like collections in cells

Related Stories

Researchers Studying Little-Known Genetic Sequences

Nov 13, 2008

(PhysOrg.com) -- University of Arizona researchers are among a group of scientists who have discovered a source of previously scarce small RNA molecules. Their finding, which was recently published in the Proceedings of th ...

Human cells can copy not only DNA, but also RNA

Aug 10, 2010

Single-molecule sequencing technology has detected and quantified novel small RNAs in human cells that represent entirely new classes of the gene-translating molecules, confirming a long-held but unproven hypothesis that ...

Silence of the genes

Jul 22, 2011

A molecular mechanism by which gene silencing is regulated at the genome-wide level in plants has been uncovered by a research team led by Motoaki Seki of the RIKEN Plant Science Center, Yokohama, Japan. ...

Recommended for you

DNA may have had humble beginnings as nutrient carrier

9 hours ago

New research intriguingly suggests that DNA, the genetic information carrier for humans and other complex life, might have had a rather humbler origin. In some microbes, a study shows, DNA pulls double duty ...

Central biobank for drug research

9 hours ago

For the development of new drugs it is crucial to work with stem cells, as these allow scientists to study the effects of new active pharmaceutical ingredients. But it has always been difficult to derive ...

User comments : 2

Adjust slider to filter visible comments by rank

Display comments: newest first

wealthychef
5 / 5 (1) Feb 29, 2012
Good. It seems to me the model that says "We are our DNA" is way too simplistic.
Jeddy_Mctedder
1 / 5 (3) Feb 29, 2012
long gone are the days where they refered to non-coding dna as 'JUNK"
hahah.