Forum für Wissenschaft, Industrie und Wirtschaft

Hauptsponsoren:     3M 
Datenbankrecherche:

 

A class of RNA molecules protects germ cells from damage, Penn vet researchers show

16.11.2012
Passing one's genes on to the next generation is a mark of evolutionary success. So it makes sense that the body would work to ensure that the genes the next generation inherits are exact replicas of the originals.

New research by biologists at the University of Pennsylvania School of Veterinary Medicine has now identified one way the body does exactly that. This protective role is fulfilled in part by a class of small RNA molecules called pachytene piwi-interacting RNAs, or piRNAs.

Without them, germ-cell development in males comes to a halt. Because these play such an important role in allowing sperm to develop normally, the research indicates that defects in these molecules or the molecules with which they interact may be responsible for some cases of male infertility.

Jeremy Wang, an associate professor of developmental biology and director of the Center for Animal Transgenesis and Germ Cell Research at Penn Vet, and Ke Zheng, a postdoctoral researcher in Wang's lab, authored the study, which appears in PLOS Genetics.

Scientists know of 8 million different piRNAs in existence; they are the most abundant type of small non-coding RNA. The molecule piRNA gets its name because it forms complexes with piwi proteins. Earlier work had indicated that these piwi-piRNA complexes suppress the activity of transposable elements or "jumping genes," which are stretches of DNA that can change position and cause potentially damaging genetic mutations. These sequences are also known as transposons.

"There are about 50 human diseases caused by transposable elements, so it's important for the body to have a way to try to repress them," Wang said.

This transposon-suppressing activity had been confirmed in a group of piRNAs called pre-pachytene piRNAs, which are expressed before meiosis, the unique process by which germ cells divide. But Zheng and Wang wanted to investigate if a separate group of piRNAs that emerge during meiosis, called pachytene piRNAs, were also required for "silencing" transposons.

Working in male mice, the researchers manipulated an enzyme called MOV10L1, which is known to interact with piwi proteins and is believed to help produce piRNA molecules. They created a mutant mouse in which they could selectively inactivate MOV10L1 at specific stages before, during and after meiosis. The mice that lost the function of MOV10L1 before or at the pachytene stage of meiosis were sterile. When Zheng and Wang examined their germ cells more closely, they found that spermatogenesis had apparently come to a halt at the post-meiotic stage: Early stages of the germ cells were present, but the mice completely lacked mature sperm.

Further experiments allowed Zheng and Wang to pinpoint that MOV10L1 was playing a critical role at the pachytene stage. MOV10L1 mutants lacked pachytene piRNAs, but their levels of pre-pachytene piRNAs were unaffected, as the mutation was "turned on" after they had already been produced.

The researchers also found that, in the MOV10L1 mutants, piwi proteins congregated together along with mitochondria, suggesting that mitochondria may be involved in the generation or organization of pachytene piRNAs. Furthermore, the spermatids, or early-stage sperm, of the mutants had severe DNA damage. While the researchers suspected that the damage may have been caused because of transposons that had been freed from repression in the absence of piRNAs, they actually found that two common transposable elements were not de-repressed in the mutants. They also found a build-up of pachytene piRNA precursors in the testes of the mutants. Their findings raise the possibility that there is another mechanism by which damage occurs.

"It could be the accumulation of precursor molecules is causing some of the damage," Wang said.

This new function for MOV10L1, in playing an essential role in producing pachytene piRNAs, gives researchers a greater understanding of germ-cell development.

"This is the first time we've shown that pachtyene piRNA is required for maintaining genome integrity in the post-meiotic germ cells," Wang said. "It turns out that MOV10L1 is a master regulator of the piRNA pathway and is required for the production of all piRNAs, both pre-pachytene and pachytene."

Any disruptions to this "master regulator" role, therefore, could lead to problems.

"I think we're just beginning to appreciate the significance of this pathway," Wang said. "Mutations at various points in the pathway could lead to infertility."

This research was supported by the National Institutes of Health's National Institute of Child Health and Human Development.

Katherine Unger Baillie | EurekAlert!
Further information:
http://www.upenn.edu

More articles from Life Sciences:

nachricht Northwestern scientists develop first liquid nanolaser
27.04.2015 | Northwestern University

nachricht Why do animals fight members of other species?
24.04.2015 | University of California - Los Angeles

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Hummelgenom entschlüsselt

Eine Kollaboration von Forschenden unter ETH-Federführung hat das Genom von zwei kommerziell bedeutenden Hummelarten aufgeklärt. Die Resultate bieten unerwartete Einblicke in Ökologie und Evolution der Hummeln und auch der Honigbiene.

Hummeln gelten als friedfertig und fleissig. Nicht zuletzt seit es weltweit mit der Honigbiene bergab geht, ist der kommerzielle Wert dieser Insekten...

Im Focus: Elektromobilität: Ultraleichtes Kraftpaket für das elektrische Fliegen

Siemens hat einen einzigartigen Elektromotor entwickelt, der hohe Leistung mit einem minimalen Gewicht kombiniert. Durch konsequente Optimierung aller Komponenten stellt der neue Antrieb in seiner Klasse einen Weltrekord beim Leistungsgewicht auf. Dadurch kommt der routinemäßige Einsatz von elektrisch angetriebenen Flugzeugen oder Helikoptern einen großen Schritt näher.

Manchmal lässt sich eine technische Revolution ganz knapp in einer einzigen Zahl zusammenfassen. In diesem Fall lautet sie: fünf Kilowatt pro Kilogramm – das...

Im Focus: Fast and Accurate 3-D Imaging Technique to Track Optically-Trapped Particles

KAIST researchers published an article on the development of a novel technique to precisely track the 3-D positions of optically-trapped particles having complicated geometry in high speed in the April 2015 issue of Optica.

Daejeon, Republic of Korea, April 23, 2015--Optical tweezers have been used as an invaluable tool for exerting micro-scale force on microscopic particles and...

Im Focus: Von Innen nach Außen: Rätsel der galaktischen Scheiben gelöst

Ein Team von Astronomen unter der Leitung von Ivan Minchev, Wissenschaftler am Leibniz-Institut für Astrophysik Potsdam (AIP), hat mithilfe hochmoderner theoretischer Modelle das Rätsel um die Entwicklung der Galaxienscheiben gelöst. Die jetzt veröffentlichte Studie zeigt, dass sich Sternpopulationen gleichen Alters durch Galaxienkollisionen nach außen hin ausweiten. Ähnlich wie die Blüten einer Rose reichern sich diese Populationen schichtweise in der Galaxie an und formen so allmählich die dicke Scheibe.

„Wir können nun zum ersten Mal zeigen, dass dicke Scheiben nicht nur aus alten Sterngenerationen bestehen, sondern – in einem größeren Abstand zum...

Im Focus: NOAA, Tulane identify second possible specimen of 'pocket shark' ever found

Pocket sharks are among the world's rarest finds

A very small and rare species of shark is swimming its way through scientific literature. But don't worry, the chances of this inches-long vertebrate biting...

Alle Focus-News des Innovations-reports >>>

Anzeige

Anzeige

IHR
JOB & KARRIERE
SERVICE
im innovations-report
in Kooperation mit academics
Veranstaltungen

Evolution von Materialhybridkonzepten

27.04.2015 | Veranstaltungen

Schall und Schwingung

27.04.2015 | Veranstaltungen

Energiemanager diskutieren über Zukunft des kommunalen Energiemanagements

27.04.2015 | Veranstaltungen

 
B2B-VideoLinks
Weitere VideoLinks >>>
Aktuelle Beiträge

Innovatives Hausbaukonzept aus Plastikelementen

27.04.2015 | Architektur Bauwesen

Starke Sache – Neueste Erkenntnisse zur Muskelfunktion

27.04.2015 | Biowissenschaften Chemie

INTERGEO positioniert UAS-Aussteller neu

27.04.2015 | Messenachrichten