Technique provides snapshot of all genes in human genome

Dec 17, 2008 By Krishna Ramanujan
This graphic shows polymerases on one strand of DNA (red) pausing during the transcription process, but some polymerases start moving again, travel through and transcribe the gene. Polymerases on the opposite strand (blue) travel in the opposite direction and also pause but do not travel significantly farther. Image: Lis Lab

(PhysOrg.com) -- Like Silly Putty lifting an imprint of the Sunday comics off a newspaper, complex enzymes called RNA polymerases lift information off DNA strands. The polymerases then transcribe those genetic instructions onto RNA for making proteins that cells use for basic functions.

In the Dec. 19 issue of Science, Cornell researchers report on a new technique that takes a snapshot of all the locations on the human genome where RNA polymerases actively transcribe genes. The method provides a new and highly sensitive way to pinpoint all the active and silent genes in the human genome.

The researchers also report on a new mechanism: Scientists always thought that RNA polymerases read DNA in one direction, by starting at a bit of DNA at the front of a gene -- the so-called promoter -- and moving to the end of the gene. But the new polymerase maps reveal that polymerases also appear on the other side of the promoter and run in the opposite direction.

"We always thought that polymerases followed one direction, but now we have polymerases going both ways," said John Lis, the paper's senior author and the Barbara McClintock Professor of Molecular Biology and Genetics at Cornell.

The polymerases going forward follow through to the end of the gene and transcribe the information for making proteins, but for reasons yet unknown, polymerases going in the opposite direction travel only a short distance and then stop. Researchers hypothesize that these opposite-facing polymerases could be holding open a segment of DNA for transcription.

The researchers also observed that the transcription process pauses because polymerases accumulate near the promoter before moving to the end of the gene. The pause may have a structural function, the researchers suggest, to hold open the site for other polymerases to enter. The pause seems to occur at genes that respond to signals (called regulated genes) and could allow time to prepare the gene for a rapid and coordinated response to a signal. Or, a pause may be necessary to make sure that all the necessary components are in place for proper transcription.

"A pause can likely be serving a different role at different genes," said Josh Waterfall, a postdoctoral researcher in Lis' lab and a co-author of the paper. "It's only in the last few years that experiments suggest these pauses are a common pattern on a lot of genes." The new study confirms that the high frequency of locations where polymerases build up, as seen in other studies, are sites where transcription pauses.

Leighton Core, a graduate student in Lis' lab and the paper's lead author, developed the new mapping technique by modifying an older technique. "The assay is actually around 30 years old, but it traditionally only measured the polymerases locations at small discrete units," he said. "But we were able to adapt the assay to measure actively engaged polymerases across the human genome."

This paper is one of four simultaneous papers appearing in Science that discuss these divergent polymerases for the first time. The papers have been online at Science Express since Dec. 4.

Provided by Cornell University

Explore further: South American parrot in trouble: researchers

Related Stories

A better way to build DNA scaffolds

May 06, 2015

Imagine taking strands of DNA - the material in our cells that determines how we look and function - and using it to build tiny structures that can deliver drugs to targets within the body or take electronic ...

How does a mobile DNA sequence find its target?

May 05, 2015

To understand how transposable elements shape genomes, where they are maintained over generations, it is vital to discover the mechanisms behind their targeted integration. Researchers from the Laboratoire ...

How an RNA gene silences a whole chromosome

Apr 27, 2015

Researchers at Caltech have discovered how an abundant class of RNA genes, called long non-coding RNAs (lncRNAs, pronounced link RNAs) can regulate key genes. By studying an important lncRNA, called Xist, ...

How RNA machinery navigates our genomic obstacle course

Apr 24, 2015

Once upon a time, scientists thought RNA polymerase—the molecule that kicks off protein synthesis by transcribing DNA into RNA—worked like a wind-up toy: Set it down at a start site in our DNA and it ...

Recommended for you

South American parrot in trouble: researchers

4 hours ago

A South American parrot with a wine-colored chest is in deep trouble, with its population down to some 3,000 and a habitat reduced to a speck of what it once was, researchers said Tuesday.

Protecting South America's iconic golden dorado fish

4 hours ago

A new study launched this month by University of Massachusetts Amherst fisheries biologist Andy J. Danylchuk, in collaboration with Argentina's Ministry of Environment and regional partners including Juramento ...

Galapagos volcano calms, pink iguanas out of danger

7 hours ago

A volcano in the Galapagos Islands whose fiery eruption raised fears for the world's only population of pink iguanas has calmed, sparing the unique critters from danger, officials said Tuesday.

User comments : 0

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.