Featured Research

from universities, journals, and other organizations

Specific Small RNA Pathways Protect Germ Line From Transposons

May 5, 2009
Cold Spring Harbor Laboratory
Animal germ line cells, such as sperm and ova, protect their genomes against transposon-inflicted damage via an immune system operated by a family of proteins called Piwi and Piwi-interacting RNA molecules (piRNAs). Scientists now show that in the fruit fly ovary, somatic cells that surround germ cells also have a piRNA pathway, although a slightly different one, that specifically protects their genomes against transposons called gypsy elements.

Cells of higher organisms are in a constant struggle against some of their own DNA – repeated bits of DNA sequence called transposons that have infiltrated host genomes over the eons. Transposons damage the rest of the genome when they copy themselves and jump into new genomic sites.

Related Articles

To protect themselves from these genetic parasites, animal germ line cells such as sperm and eggs, whose mission is to pass on undamaged DNA to the next generation, have developed a molecular immune system. This system is operated by an army of small RNA molecules called Piwi-interacting RNAs (piRNAs) and a set of proteins belonging to the Piwi family.

In a new study appearing in the May 1 issue of Cell, Professor Gregory Hannon, Ph.D., of Cold Spring Harbor Laboratory (CSHL), and his team, report that in the ovaries of fruit flies, non-germ line, or "somatic cells" that surround germ line cells have also developed an anti-transposon defense system.

The piRNAs and protein components of this somatic system, however, are distinct from their counterparts within germ line cells, the researchers show. The system that defends somatic cells specifically guards against a particular class of transposon called gypsy elements. These bits of DNA mobilize themselves for attacks in a way that differs from that used by transposons active in germ cells.

Two distinct piRNA pathways in the ovary

Many transposons propagate themselves by first getting copied or transcribed into RNA, which in turn gets copied back into a new DNA segment. That new segment is then inserted into a new genomic location. Gypsy elements similarly begin to mobilize by first converting into RNA, but are then processed into virus-like particles that propagate by infecting neighboring cells. "But the step in which the transposon is transcribed to RNA is also an Achilles heel," notes Hannon. "Cells are able to defend themselves by targeting the transposons during this intermediate RNA step."

The cell's counter-response is a form of defense called RNA interference, in which piRNAs partner with members of the Piwi protein family – called Argonaute3 (AGO3), Aubergine (Aub) and Piwi – to "silence" transposons. These three proteins act as molecular "scissors" that slice up transposon RNA that their piRNA "guides" lead them to.

While all three Piwi proteins – AGO3, Aub and Piwi – are found in germ cells, Hannon and the CSHL team found only the Piwi protein in somatic cells that surround germ line cells. This suggested to them possible differences in the architecture of the piRNA pathway between the two cell types.

Separating germ line and somatic cells

But how to separate RNA and protein components of the germ cells from that of the surrounding somatic cells? "We simply exploited the fruit fly's natural biology to do this," says Colin Malone, a graduate student in the Hannon lab who led the current study. When fruit fly germ cells develop into embryos, they shed the surrounding somatic cells. A newly laid egg thus includes RNA and protein components that are present only in the germ line, and not the ovary's somatic tissue.

By comparing piRNAs in embryos to those in the ovary, then, the CSHL team discovered that while germ cells contained piRNAs targeted to a variety of transposons, the somatic piRNA fraction utilizes only the Piwi protein to selectively suppress gypsy transposons.

The somatic cells therefore appear to make use of a simplified form of the piRNA "scaffold," employing only one Piwi protein and particular piRNAs to defend against a single class of transposons – the gypsy elements, which might try to gain access to adjacent germ cells through their ability to package themselves like a virus.

Somatic cells are defended by the flamenco piRNA cluster

piRNAs arise from so-called 'transposon graveyards' in the genome, where transposon remnants that can no longer jump are clustered. Scientists speculate that these clusters persist in genomes to provide host cells with a "memory" of previous transposon exposure.

"Once a transposon jumps into a piRNA cluster, that transposon's future is grim," says Malone. The cell will immediately make piRNAs that target this transposon, so that any future activity is immediately blocked.

Hannon's lab had previously found that piRNAs generated from most clusters get amplified in number via a "ping-pong" mechanism – reciprocal cycles of cleavage of RNA molecules by pairs of Piwi-family proteins. They now find that only germ cells use this mechanism to generate and amplify their piRNA stockpile.

In somatic cells, however, the scientists found that the piRNAs utilized by the sole Piwi protein arise from a single cluster called flamenco. This cluster, the authors suggest, appears to be conserved – unchanged over evolutionary time – in most Drosophila species. This in fact represents tens of millions of years of evolution.

The significance of the finding

"The gypsy family may have evolved their own mobilization strategy in the soma to evade the extensive anti-transposon surveillance system already in place in the neighboring germ cells," explains Malone. "The somatic cells, in turn, might have adapted a distinct piRNA pathway, centered on Piwi and the flamenco cluster, as a counter-evolutionary move to cope with this unique threat."

Over the years, fruit fly researchers have uncovered a number of genomic mutations that lead to sterility and abnormal development. Since these defects could have been caused by unchecked transposon activity, mutant flies are a good experimental resource to uncover exactly how piRNA pathways work and how they might get disrupted.

The Hannon team has analyzed eight such mutants, showing how the genes disrupted in each mutant impact the piRNA pathway and how it alters the type and number of piRNAs that cells are able to generate.

"We are beginning to paint a broad picture of how the piRNA pathway has been genetically stitched together," says Hannon. "This work brings decades of research into a cohesive model that can be used as the starting point to understand how each gene that contributes to a fly's biological phenotype is acting at the molecular level."

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. Colin D. Malone, Julius Brennecke, Monica Dus, Alexander Stark, W. Richard McCombie, Ravi Sachidanandam, and Gregory J. Hannon. Specialized piRNA Pathways Act in Germline and Somatic Tissues of the Drosophila Ovary. Cell, May 1, 2009

Cite This Page:

Cold Spring Harbor Laboratory. "Specific Small RNA Pathways Protect Germ Line From Transposons." ScienceDaily. ScienceDaily, 5 May 2009. <www.sciencedaily.com/releases/2009/05/090505153631.htm>.
Cold Spring Harbor Laboratory. (2009, May 5). Specific Small RNA Pathways Protect Germ Line From Transposons. ScienceDaily. Retrieved March 30, 2015 from www.sciencedaily.com/releases/2009/05/090505153631.htm
Cold Spring Harbor Laboratory. "Specific Small RNA Pathways Protect Germ Line From Transposons." ScienceDaily. www.sciencedaily.com/releases/2009/05/090505153631.htm (accessed March 30, 2015).

Share This

More From ScienceDaily

More Health & Medicine News

Monday, March 30, 2015

Featured Research

from universities, journals, and other organizations

Featured Videos

from AP, Reuters, AFP, and other news services

Soda, Salt and Sugar: The Next Generation of Taxes

Soda, Salt and Sugar: The Next Generation of Taxes

Washington Post (Mar. 30, 2015) — Denisa Livingston, a health advocate for the Dinι Community Advocacy Alliance, and the Post&apos;s Abby Phillip discuss efforts around the country to make unhealthy food choices hurt your wallet as much as your waistline. Video provided by Washington Post
Powered by NewsLook.com
UnitedHealth Buys Catamaran

UnitedHealth Buys Catamaran

Reuters - Business Video Online (Mar. 30, 2015) — The $12.8 billion merger will combine the U.S.&apos; third and fourth largest pharmacy benefit managers. Analysts say smaller PBMs could also merge. Fred Katayama reports. Video provided by Reuters
Powered by NewsLook.com
S. Leone in New Anti-Ebola Lockdown

S. Leone in New Anti-Ebola Lockdown

AFP (Mar. 28, 2015) — Sierra Leone imposed a three-day nationwide lockdown Friday for the second time in six months in a bid to prevent a resurgence of the deadly Ebola virus. Duration: 01:17 Video provided by AFP
Powered by NewsLook.com
These Popular Antibiotics Can Cause Permanent Nerve Damage

These Popular Antibiotics Can Cause Permanent Nerve Damage

Newsy (Mar. 27, 2015) — A popular class of antibiotic can leave patients in severe pain and even result in permanent nerve damage. 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.


Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News


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