Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

A milestone in small RNA biology: piRNA biogenesis from start to finish

17.11.2016

Organisms are in a constant battle against viruses, or transposable elements, which invade their genomes. Among their most effective weapons are silencing pathways that use small RNAs to selectively target invading nucleic acids for their destruction. The molecular understanding of these defense systems has revolutionized modern molecular biology, as they are the basis for powerful genome editing and gene silencing methods such as CRISPR/Cas9 or RNA interference. Scientists from the Institute of Molecular Biotechnology in Vienna (IMBA) have now unravelled the precise mechanisms by which germline cells produce a class of small RNAs, called piRNAs, that control transposon silencing in animals.

PIWI-interacting RNAs, or piRNAs for short, are a class of ‘small regulatory RNAs’—tiny pieces of nucleic acid just 22–30 nucleotides in length. They may be small, but with their associated Argonaute proteins, piRNAs have the power to ‘silence’ transposable elements, so called egoistic genes found in the genomes of plants, fungi, and animals. piRNA-guided silencing can act on chromatin to block transposon transcription, or by destroying transposon mRNAs in order to block their translation into proteins.


A melody played by two hands: Two evolutionarily ancient parallel pathways make up the 3’end of piRNAs. This illustration by Beata Mierzwa compares piRNA 3’ end formation to a piece of music where two pathways - involving Zucchini and Nibbler - play simultaneously to generate a diverse pool of piRNAs. The sheet music encodes characteristic nucleotide patters of the emerging piRNAs.

Although scientists understand quite well how piRNAs repress gene expression, until now, it has been much less clear how piRNAs are actually made. In a milestone research paper published in Nature, scientists from the Institute of Molecular Biotechnology in Austria (IMBA) have painstakingly unravelled the sequence of events that generate piRNAs with a defined length and sequence, a central requirement to define the target spectrum of the silencing system.

Mystery of piRNA biogenesis explained
Julius Brennecke, one of the paper’s senior authors, explained:
“We already knew that piRNAs are formed from longer RNA species that are chopped up into pieces by Argonaute proteins or a protein called Zucchini. This forms the 5' ends of so-called pre-piRNAs, which are loaded into Argonaute proteins and subsequently trimmed and modified to yield mature piRNAs. As we had a fairly good understanding of the generation of piRNA 5' ends, our group focused on the 3' ends, a process that was not understood for nearly ten years.”

Using the common fruit fly Drosophila melanogaster, a major genetic model organism, IMBA scientists Rippei Hayashi and Jakob Schnabl—both first authors of the article—revealed that piRNA 3' end formation in fact follows one of two parallel pathways.

“Once biogenesis is initiated, some piRNA 3' ends are actually generated by Zucchini, the endonuclease that is primarily known to generate piRNA 5' ends”, said last author Stefan Ameres. “But Zucchini explains the biogenesis of only a subset of piRNAs. We then discovered that the exonuclease Nibbler is a second key-enzyme that can form piRNA 3' ends and realized that two genetically separated pathways act in parallel in the cell. This was a true deja vu as we also found Nibbler to mature some microRNAs, yet another class of small RNA molecules, during my postdoctoral work.”

Two parallel pathways in tune
Beyond unravelling these pathways, their place of action, and their implications for downstream gene regulatory mechanisms, the team also made some interesting observations that might provide clues as to the evolution of small RNA biogenesis. “The nucleases we’ve identified in this study have homologs in animals ranging from sponges to human. Interestingly, some notable exceptions are apparent. Nematode worms, for example, have lost the Zucchini enzyme, and mosquitos from the Anopheles genus have lost Nibbler. Whether here other piRNA trimming mechanisms exist or whether in these species the two-pathway model is reduced to one, is unclear. Remarkably, upon simultaneous ablation of Zucchini and Nibbler in Drosophila, piRNAs can still be generated, in this case by closely spaced piRNA-guided Argonaute cleavage events. This Argonaute-only pathway might be the ancient piRNA generating system, onto which sophisticated nucleases like Zucchini and Nibbler were added later to enhance efficiency and accuracy of piRNA biogenesis,” concludes Julius Brennecke.

Original publication:
“'Genetic and mechanistic diversity of piRNA 3'-end formation'”, Rippei Hayashi, Jakob Schnabl, Dominik Handler, Fabio Mohn, Stefan L. Ameres & Julius Brennecke, Nature, November 16, 2016; doi: 10.1038/nature20162

Weitere Informationen:

http://de.imba.oeaw.ac.at/index.php?id=516

Mag. Ines Méhu-Blantar | idw - Informationsdienst Wissenschaft

More articles from Life Sciences:

nachricht Researchers identify how bacterium survives in oxygen-poor environments
22.11.2017 | Columbia University

nachricht Researchers discover specific tumor environment that triggers cells to metastasize
22.11.2017 | University of California - San Diego

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Nanoparticles help with malaria diagnosis – new rapid test in development

The WHO reports an estimated 429,000 malaria deaths each year. The disease mostly affects tropical and subtropical regions and in particular the African continent. The Fraunhofer Institute for Silicate Research ISC teamed up with the Fraunhofer Institute for Molecular Biology and Applied Ecology IME and the Institute of Tropical Medicine at the University of Tübingen for a new test method to detect malaria parasites in blood. The idea of the research project “NanoFRET” is to develop a highly sensitive and reliable rapid diagnostic test so that patient treatment can begin as early as possible.

Malaria is caused by parasites transmitted by mosquito bite. The most dangerous form of malaria is malaria tropica. Left untreated, it is fatal in most cases....

Im Focus: A “cosmic snake” reveals the structure of remote galaxies

The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.

Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...

Im Focus: Visual intelligence is not the same as IQ

Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.

That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...

Im Focus: Novel Nano-CT device creates high-resolution 3D-X-rays of tiny velvet worm legs

Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.

During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....

Im Focus: Researchers Develop Data Bus for Quantum Computer

The quantum world is fragile; error correction codes are needed to protect the information stored in a quantum object from the deteriorating effects of noise. Quantum physicists in Innsbruck have developed a protocol to pass quantum information between differently encoded building blocks of a future quantum computer, such as processors and memories. Scientists may use this protocol in the future to build a data bus for quantum computers. The researchers have published their work in the journal Nature Communications.

Future quantum computers will be able to solve problems where conventional computers fail today. We are still far away from any large-scale implementation,...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Ecology Across Borders: International conference brings together 1,500 ecologists

15.11.2017 | Event News

Road into laboratory: Users discuss biaxial fatigue-testing for car and truck wheel

15.11.2017 | Event News

#Berlin5GWeek: The right network for Industry 4.0

30.10.2017 | Event News

 
Latest News

UCLA engineers use deep learning to reconstruct holograms and improve optical microscopy

22.11.2017 | Medical Engineering

Watching atoms move in hybrid perovskite crystals reveals clues to improving solar cells

22.11.2017 | Materials Sciences

New study points the way to therapy for rare cancer that targets the young

22.11.2017 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>