Researchers at IMBA - Institute of Molecular Biotechnology of the Austrian Academy of Sciences - unveil novel mechanism for gene expression.
DNA in all organisms from yeast to humans encodes the genes that make it possible to live and reproduce. But these beneficial genes make up only 2% of our DNA. In fact, more than two-thirds of our genome is populated by selfish genes that only care about their own replication – so-called genetic parasites.
The protein "Moonshiner" triggers RNA transcription within heterochromatin - depicted as a sea of densely packed histones. Drawing by Beata Mierzwa (beatascienceart.com)
Scattered throughout the genomes of plants, fungi, and animals, they can jump from one genomic location to another. Although they can be important for generating diversity in the genome, they can also cause lethal mutations or sterility.
Just as bacteria use the CRISPR/Cas9 system to identify and cleave viruses invading their DNA, eukaryotic cells have developed various strategies to protect the genome and silence these selfish genetic parasites. Small regulatory RNAs govern many of these genome-defense mechanisms and have also yielded major biotechnological innovations.
Solving an evolutionary “chicken and egg” dilemma
One important pathway that maintains the genomic integrity of animals is the piRNA pathway. This system is active in germ cells and utilizes small snippets of RNA—so called piRNAs—which fit like mirror images onto the transcripts of selfish sequences and thereby initiate silencing with their associated Argonaut proteins.
The Brennecke lab at IMBA has been rigorously exploring these RNA-based self-defense mechanisms in fruit flies, using cutting-edge next generation sequencing. The source of piRNAs is within silenced regions containing the selfish elements. This organization established an evolutionary “chicken and egg” dilemma: How could piRNAs be generated from the very regions that they silence? In their current Nature publication, Brennecke’s lab not only solve this enigma but also describe a completely new mechanism for gene-expression.
Moonshiner: There is always a way around
The newly discovered pathway is centered around a protein called moonshiner. Moonshiner is related to basal transcription factors, and interacts with Rhino, a protein bound to heterochromatin at the selfish genes. Rhino recruits Moonshiner to the heterochromatic region, and Moonshiner initiates assembly of the RNA polymerase II pre-initiation complex, that catalyzes the transcription.
Therefore, gene expression is activated in an otherwise silent region via a different code embedded in histone marks rather than DNA sequence. The findings show that piRNAs are transcribed by bending the classical rules of gene activation, combining elements of standard gene activation with gene silencing.
“The pathway, that is active in the piRNA clusters – where the piRNAs are born – literally hacks the gene machinery by combining two different systems, gene activation with gene silencing, just like furniture can be repurposed by IKEA hacking,” illustrates Peter Andersen, Postdoc at IMBA and first author of the paper. The moonshiner pathway thus reveals how cells can utilize heterochromatin for transcription.
“Cells have developed strategies to bypass conventional pathways. The current findings are not only essential to understand the arm´s race between useful genes and the selfish genes that have shaped and still drive evolutionary processes, they also contribute to understanding gene expression in a holistic way,” says Julius Brennecke, IMBA group leader and last author.
'A heterochromatin-dependent transcription machinery drives piRNA expression', Andersen at al.,
Nature; DOI: 10.1038/nature23482
IMBA - Institute of Molecular Biotechnology is one of the leading biomedical research institutes in Europe focusing on cutting-edge functional genomics and stem cell technologies. IMBA is located at the Vienna Biocenter, the vibrant cluster of universities, research institutes and biotech companies in Austria. IMBA is a subsidiary of the Austrian Academy of Sciences, the leading national sponsor of non-university academic research.
About the Vienna BioCenter
The Vienna BioCenter (VBC) is a leading life sciences location in Europe, offering an extraordinary combination of research, education and business on a single campus. About 1,700 employees, more than 1,300 students, 86 research groups, 17 biotech companies, and scientists from more than 40 nations create a highly dynamic environment.
Mag. Ines Méhu-Blantar | idw - Informationsdienst Wissenschaft
Lethal combination: Drug cocktail turns off the juice to cancer cells
12.12.2018 | Universität Basel
Smelling the forest – not the trees
12.12.2018 | Universität Konstanz
A widely used diabetes medication combined with an antihypertensive drug specifically inhibits tumor growth – this was discovered by researchers from the University of Basel’s Biozentrum two years ago. In a follow-up study, recently published in “Cell Reports”, the scientists report that this drug cocktail induces cancer cell death by switching off their energy supply.
The widely used anti-diabetes drug metformin not only reduces blood sugar but also has an anti-cancer effect. However, the metformin dose commonly used in the...
A research team from the University of Zurich has developed a new drone that can retract its propeller arms in flight and make itself small to fit through narrow gaps and holes. This is particularly useful when searching for victims of natural disasters.
Inspecting a damaged building after an earthquake or during a fire is exactly the kind of job that human rescuers would like drones to do for them. A flying...
Over the last decade, there has been much excitement about the discovery, recognised by the Nobel Prize in Physics only two years ago, that there are two types...
What if a sensor sensing a thing could be part of the thing itself? Rice University engineers believe they have a two-dimensional solution to do just that.
Rice engineers led by materials scientists Pulickel Ajayan and Jun Lou have developed a method to make atom-flat sensors that seamlessly integrate with devices...
Scientists at the University of Stuttgart and the Karlsruhe Institute of Technology (KIT) succeed in important further development on the way to quantum Computers.
Quantum computers one day should be able to solve certain computing problems much faster than a classical computer. One of the most promising approaches is...
12.12.2018 | Event News
10.12.2018 | Event News
06.12.2018 | Event News
12.12.2018 | Health and Medicine
12.12.2018 | Physics and Astronomy
12.12.2018 | Health and Medicine