Reversing the conventional DNA wisdom

December 4, 2008

( -- The copying of DNA's master instructions into messenger molecules of RNA, a process known as DNA transcription, has always been thought to be a unidirectional process whereby a copying machine starts and moves in one direction. But in work that represents a fundamental shift in scientists' understanding of the phenomenon, MIT researchers have found evidence that two DNA copying machines frequently start from the same site and move in different directions.

MIT Institute Professor Phillip Sharp and his colleagues, who report the results in the Dec. 4 early online edition of Science, believe this new mechanism may play a role in keeping genes poised for transcription.

"People have been studying transcription for a long time and never seen this kind of transcription before," said Amy Seila, a postdoctoral associate in Sharp's lab and lead author of the paper.

DNA, which is housed within the nucleus of cells, controls cellular activity by coding for the production of enzymes and proteins. The genetic information in DNA is not directly converted into proteins, but must first be copied, i.e. transcribed, into RNA.

During normal transcription, an enzyme called RNA polymerase binds to a gene's transcription start site, and then proceeds downstream along the DNA, copying the sequence and producing messenger RNA that carries the gene's instructions.

In the new scenario, a second RNA polymerase is believed to bind near the starting point and move upstream, producing a short RNA sequence that doesn't code for any proteins.

"It looks like we have a polymerase that binds as we thought, but we also see a polymerase that appears to be pointing in the wrong direction, going upstream from the transcription start site," Seila said.

The researchers believe that upstream and downstream RNA polymerases, or divergent polymerases, are "paused" on the DNA and keeping the transcription start site open, so the gene can be easily accessed and transcribed.

The MIT team postulated this divergent transcription after discovering a new class of small RNA, which they dubbed TSSa-RNA because it is associated with transcription start sites.

The researchers found from analysis of tens of millions of short RNA sequences that many of these RNAs were clustered just upstream of gene transcription start sites, suggesting that DNA transcription is occurring in the reverse direction. Many of the genes where these short RNAs were found are very active, supporting the theory that this mechanism helps promote gene transcription.

The researchers observed this phenomenon in several kinds of cells in both humans and mice, leading them to believe that it is universal.

A paper by another researcher, John Lis of Cornell University, offers independent evidence for the same theory. In a paper also appearing online in Science this week, Lis reports finding RNA polymerases sitting on genes both upstream and downstream from transcription start sites, waiting to be activated.

Sharp's lab plans to undertake further experiments to determine what roles these transcription start site-associated RNAs play in gene regulation, and whether they might interact with other types of small RNA such as microRNA.

"This is only the beginning of the story. It's certainly not the end of the story," said Sharp.

Other authors of the paper are J. Mauro Calabrese, a former graduate student in Sharp's lab; Stuart Levine and Peter Rahl, postdoctoral associates in the Whitehead Institute; Ryan Flynn, a junior biology major; Richard Young, professor of biology and member of the Whitehead Institute; and Gene Yeo of the University of California at San Diego.

Provided by MIT

Explore further: Chemists and applied physicists observe RNA polymerase at work in real time

Related Stories

Cell aging slowed by putting brakes on noisy transcription

July 30, 2015

Working with yeast and worms, researchers found that incorrect gene expression is a hallmark of aged cells and that reducing such "noise" extends lifespan in these organisms. The team published their findings this month in ...

Researchers discover new mechanism of DNA repair

July 3, 2015

The DNA molecule is chemically unstable giving rise to DNA lesions of different nature. That is why DNA damage detection, signaling and repair, collectively known as the DNA damage response, are needed.

The hidden treasure in RNA-seq

July 1, 2015

Michael Stadler and his team at the Friedrich Miescher institute for Biomedical Research (FMI) have developed a novel computational approach to analyze RNA-seq data. By comparing intronic and exonic RNA reads, this approach ...

Recommended for you

Trade in invasive plants is blossoming

October 3, 2015

Every day, hundreds of different plant species—many of them listed as invasive—are traded online worldwide on auction platforms. This exacerbates the problem of uncontrollable biological invasions.

How much for that Nobel prize in the window?

October 3, 2015

No need to make peace in the Middle East, resolve one of science's great mysteries or pen a masterpiece: the easiest way to get yourself a Nobel prize may be to buy one.

Drone market to hit $10 billion by 2024: experts

October 3, 2015

The market for military drones is expected to almost double by 2024 to beyond $10 billion (8.9 billion euros), according to a report published Friday by specialist defence publication IHS Jane's Intelligence Review.

Fusion reactors 'economically viable' say experts

October 2, 2015

Fusion reactors could become an economically viable means of generating electricity within a few decades, and policy makers should start planning to build them as a replacement for conventional nuclear power stations, according ...


Adjust slider to filter visible comments by rank

Display comments: newest first

5 / 5 (1) Dec 04, 2008
I would be willing to bet that this new class of small RNA's may be utilized in the process of DNA transcription when an error is detected in the copy. If an error were detected, the new small RNA's may work backward until the entire gene is recopied and then pasted into the DNA molecule being transcribed.
not rated yet Dec 05, 2008
Thats not it cause the RNA is upstream of the promoter and the gene is downstream so this RNA does not contain the part of the gene to be turned into protein and therefore can't fix any errors in it.

As the genes are highly transcribed those could simply be errors of polymerases, or they can play the role of an anchor and a marker that the part of DNA is being transcribed now. Both cases could be true.

Whichever it is its certainly not a "fundamental shift in scientists' understanding of" transcription. Just new details which were obscured previously due to lack of suitable ways for analyzing RNA populations.

There will certainly be more findings like that as RNA has an unmatched potential when it comes to regulating DNA processing.

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.