Featured Research

from universities, journals, and other organizations

'Mistake' in single-cell organism actually a rewrite essential to life

Date:
October 3, 2013
Source:
Ohio State University
Summary:
A tiny but unexpected change to a segment of RNA in a single-cell organism looks a lot like a mistake, but is instead a change to the genetic information that is essential to the organism’s survival.

A tiny but unexpected change to a segment of RNA in a single-cell organism looks a lot like a mistake, but is instead a change to the genetic information that is essential to the organism's survival.

Scientists have discovered this RNA "edit" in Trypanosoma brucei, a parasite that causes sleeping sickness in Africa and Chagas disease in Latin America. Though the organism is a model system for this work, the finding could lead to a new drug target to fight the parasite if higher species don't share this genetic behavior.

Some of the organism's genetic activity was already known. In the case of gene products called tRNAs, which help assemble the amino acids that make proteins, T. brucei was known to have only one tRNA with a specific segment of RNA that ensures the tRNA's proper function. Additionally, examples of RNA editing have been discovered before.

But in this case, the way genetic information necessary for the protein production process was changed -- through a swap of three nucleotides for three others that are completely out of place -- has never been seen before.

"These are changes for which no chemistry is known and has never been described. We don't know what enzyme is involved and that is the million-dollar question: What mechanism is doing this? We haven't a clue," said Juan Alfonzo, professor of microbiology at The Ohio State University and senior author of the study.

"If the activity is unique to a trypanosome, then you have a good drug target. If it is widespread, then you have to reconsider one more time what coding sequences really mean in the sense that you can indeed change them in a very programmed fashion by activities that don't exist -- that have not been described," said Alfonzo, also an investigator in Ohio State's Center for RNA Biology.

The work is the result of Alfonzo's longtime collaboration with co-lead author Christopher Trotta, senior director of biology at PTC Therapeutics in South Plainfield, N.J.

The study appears online in the journal Molecular Cell and is scheduled for print publication on Oct. 24.

The finding was not only unexpected, but serendipitous. Alfonzo's lab was analyzing an enzyme affecting T. brucei's tRNA behavior in response to a request from Trotta, a drug developer who is considered a pioneer of research on tRNAs. To begin the analysis, Alfonzo sought to identify the intron, a specific segment of RNA, that needs to be removed before the tRNA can participate in the selection of the right amino acids during protein production.

This critical function of removing the intron is called splicing -- in essence, a pre-requisite chemical reaction affirming that tRNA can deliver the correct instructions for protein production. If a tRNA is not spliced, it will not work in protein production and the cell will die.

The trouble was, Alfonzo couldn't locate the intron that he knew was there. After multiple attempts, he found that the intron's sequence in this organism changed after transcription, the point at which a copy of RNA is made from a DNA sequence as the first step of gene expression.

This edit -- hard to find because of its odd nature -- consisted of a change to three nucleotides, the molecules that form DNA and RNA. Because of its rarity and unusual nature, it is called a noncanonical edit.

"It's noncanonical because it is not typical. It is completely not typical," Alfonzo said. "And for the first time, we show the biological significance. We show that if you don't edit, you don't splice. This editing is required for splicing, and splicing is required for functionality. Otherwise, cells die."

Previously known methods of RNA editing include deamination, the removal of sections of molecules from the RNA that change the message from the DNA, and nucleotide insertion, deletion or exchange. The editing described here is a swap of three nucleotides for three others that, according to the rules of biology, do not belong where they end up. This is why it looks like a mistake.

Colleagues have suggested that this edit should have been identified by researchers who do deep sequencing, which involves repeated readings of all nucleotides within an RNA molecule, Alfonzo noted. But he is not surprised that technology didn't yield these results.

"In massive sequencing, you match RNAs to the sequence in the genome. Any mismatch is called a sequence mistake and is thrown in the trash. So this noncanonical editing may well be in the trash bin of many of these deep sequencing researchers," he said.


Story Source:

The above story is based on materials provided by Ohio State University. Note: Materials may be edited for content and length.


Journal Reference:

  1. MaryAnneT. Rubio, Zdeněk Paris, KirkW. Gaston, IanM.C. Fleming, Paul Sample, ChristopherR. Trotta, JuanD. Alfonzo. Unusual Noncanonical Intron Editing Is Important for tRNA Splicing in Trypanosoma brucei. Molecular Cell, 2013; DOI: 10.1016/j.molcel.2013.08.042

Cite This Page:

Ohio State University. "'Mistake' in single-cell organism actually a rewrite essential to life." ScienceDaily. ScienceDaily, 3 October 2013. <www.sciencedaily.com/releases/2013/10/131003121153.htm>.
Ohio State University. (2013, October 3). 'Mistake' in single-cell organism actually a rewrite essential to life. ScienceDaily. Retrieved September 2, 2014 from www.sciencedaily.com/releases/2013/10/131003121153.htm
Ohio State University. "'Mistake' in single-cell organism actually a rewrite essential to life." ScienceDaily. www.sciencedaily.com/releases/2013/10/131003121153.htm (accessed September 2, 2014).

Share This




More Health & Medicine News

Tuesday, September 2, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

U.N. Says Ebola Travel Restrictions Will Cause Food Shortage

U.N. Says Ebola Travel Restrictions Will Cause Food Shortage

Newsy (Sep. 2, 2014) The U.N. says the problem is two-fold — quarantine zones and travel restrictions are limiting the movement of both people and food. Video provided by Newsy
Powered by NewsLook.com
Get on Your Bike! London Cycling Popularity Soars Despite Danger

Get on Your Bike! London Cycling Popularity Soars Despite Danger

AFP (Sep. 1, 2014) Wedged between buses, lorries and cars, cycling in London isn't for the faint hearted. Nevertheless the number of people choosing to bike in the British capital has doubled over the past 15 years. Duration: 02:27 Video provided by AFP
Powered by NewsLook.com
Can You Train Your Brain To Eat Healthy?

Can You Train Your Brain To Eat Healthy?

Newsy (Sep. 1, 2014) New research says if you condition yourself to eat healthy foods, eventually you'll crave them instead of junk food. Video provided by Newsy
Powered by NewsLook.com
We've Got Mites Living In Our Faces And So Do You

We've Got Mites Living In Our Faces And So Do You

Newsy (Aug. 30, 2014) A new study suggests 100 percent of adult humans (those over 18 years of age) have Demodex mites living in their faces. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins