Featured Research

from universities, journals, and other organizations

Scientists uncover alternative pathway of microRNA generation

Date:
May 3, 2010
Source:
Cold Spring Harbor Laboratory
Summary:
MicroRNAs control gene expression with the help of a unique class of proteins called Argonautes. Researchers now report that in animal cells, one of Argonautes, called Ago2, has a different role -- it helps generate microRNAs instead. The study points to an alternative pathway of microRNA generation.

MicroRNAs are small bits of RNA within cells that wield enormous power. They influence virtually every biological process by controlling the "expression" of genes. Helping them in exerting this control is a unique class of proteins called Argonautes.

Related Articles


Cold Spring Harbor Laboratory (CSHL) researchers led by Professor and HHMI investigator Gregory Hannon, Ph.D, now report that in animal cells, one of Argonautes, called Ago2, has a different role -- it helps generate microRNAs instead. The study, which appears online, ahead of print in Nature on April 27th points to an alternative pathway of microRNA generation that the team discovered by analyzing a microRNA molecule produced in developing red blood cells.

In 2004, a team led by Hannon and Leemor Joshua-Tor, another CSHL Professor discovered that Ago2 functions as a slicer enzyme that chops up its targets -- messenger RNAs encoded by genes -- by using small RNA molecules (for example, microRNAs) as guides to home in on the correct messenger RNAs. The team's subsequent studies revealed a possible role for this slicing, or catalytic, activity of Ago2 in mammalian oocytes.

"But we found that although Ago2 is critical for the viability of embryos during development in mice, Ago2's microRNA partners generally undertake gene regulation during embryogenesis in ways that do not require the catalytic activity of this enzyme" explains Hannon. "So the basis of the evolutionary pressure to retain this catalytic ability was a mystery to us."

Engineering mice with catalytically inactive Ago2, the team has now found that mice give birth to progeny that die a few hours after birth, showing symptoms of anemia. "These mutant animals have only 50% of the normal level of red blood cells at birth," says Sihem Cheloufi, a Stony Brook University graduate student pursuing her doctoral research in Hannon's lab. "Their lack of catalytically active Ago2 hampers their normal postnatal development."

Cheloufi and her colleagues have traced a molecular cause of this lethal defect to a single microRNA, miR-451, that's present in normal mice but missing in the mice that lack catalytically active Ago2. Further experiments showed that the absence of miR-451 in the mutant mice was due not to a defect in its production but the subsequent "maturation" steps that produce a functional microRNA molecule.

Most known microRNAs, which are about 24 "letters" or nucleotides long, are much longer when they are produced and "mature" -- or get trimmed down to size -- via a two-step process. After the first trimming step by an enzyme called Drosha, the shortened RNA molecule folds on itself like a hairpin.

Normally, the hairpin's curve, called the "loop" is subsequently cut out by another enzyme called Dicer, leaving behind a double-stranded "stem." This is the mature microRNA that gets picked up by Ago2. One strand is eventually discarded; the other Ago2-bound strand is ready to seek out and trigger the destruction of its messenger RNA target.

Hannon's team has found however, that miR-451 maturation proceeds via a different pathway, where the Dicer step is skipped and the immature hairpin is directly loaded into Ago2. "Ago2 then essentially performs its slicing job to complete the maturation of this microRNA," Cheloufi explains. The team attributes the ability to Ago2 to bind to the immature miR-451 hairpin to its unique structure that is also highly conserved in vertebrates.

"The existence of this alternative pathway explains some of the evolutionary pressure to maintain a catalytically active Argonaute protein in animals," says Hannon. His team is now hunting for other RNA molecules that might be similarly generated and that might be critical for normal embryogenesis.


Story Source:

The above story is based on materials provided by Cold Spring Harbor Laboratory. Note: Materials may be edited for content and length.


Journal Reference:

  1. Sihem Cheloufi, Camila O. Dos Santos, Mark M. W. Chong, Gregory J. Hannon. A dicer-independent miRNA biogenesis pathway that requires Ago catalysis. Nature, 2010; DOI: 10.1038/nature09092

Cite This Page:

Cold Spring Harbor Laboratory. "Scientists uncover alternative pathway of microRNA generation." ScienceDaily. ScienceDaily, 3 May 2010. <www.sciencedaily.com/releases/2010/04/100428093929.htm>.
Cold Spring Harbor Laboratory. (2010, May 3). Scientists uncover alternative pathway of microRNA generation. ScienceDaily. Retrieved April 24, 2015 from www.sciencedaily.com/releases/2010/04/100428093929.htm
Cold Spring Harbor Laboratory. "Scientists uncover alternative pathway of microRNA generation." ScienceDaily. www.sciencedaily.com/releases/2010/04/100428093929.htm (accessed April 24, 2015).

Share This


More From ScienceDaily



More Plants & Animals News

Friday, April 24, 2015

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Dispute Flares Over Controversial Thai Temple Tigers

Dispute Flares Over Controversial Thai Temple Tigers

AFP (Apr. 24, 2015) Thai wildlife officials begin a headcount of nearly 150 tigers kept by monks at a temple which has become the centre of a dispute over the welfare of the animals. Video provided by AFP
Powered by NewsLook.com
College Kegger: University Gets in on Craft Brew

College Kegger: University Gets in on Craft Brew

AP (Apr. 24, 2015) Theres never been a shortage of beer on college campuses. But students at Cal Poly-Pomona are learning how to brew, serving their product to classmates, and hoping to land jobs in craft breweries when they graduate. (April 24) Video provided by AP
Powered by NewsLook.com
Cambodian Butterflies Help Villagers Make a Living

Cambodian Butterflies Help Villagers Make a Living

AFP (Apr. 24, 2015) Cambodia&apos;s Banteay Srey Butterfly Centre is the largest of its kind in Southeast Asia. As well as educating tourists about the creatures, it also offers a source of income to nearby villagers, who are paid to breed local species. Duration: 02:04 Video provided by AFP
Powered by NewsLook.com
3D Food Printing: The Meal of the Future?

3D Food Printing: The Meal of the Future?

AP (Apr. 23, 2015) Developers of 3D food printing hope the culinary technology will revolutionize the way we cook and eat. (April 23) Video provided by AP
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:

Strange & Offbeat Stories


Plants & Animals

Earth & Climate

Fossils & Ruins

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