Compared to other organisms, the genome of eukaryotes is enormous. However, of the roughly 3 billion base pairs that make up the human genome, only 1-2% encode genes. The vast majority of the genome is not used to make proteins. Scattered within the previously designated ‘junk DNA’ are transposable elements, genetic remnants from evolution and parts of retroviruses that inserted their genetic code into the human genome millennia ago. Because transposons can catalyze their own relocation within the genome, they have the potential to introduce mutations, posing a danger to genomic integrity. Cells have therefore evolved mechanisms to control transposable elements. “This is especially important in the germline, where any mutation will be passed on to future generations”, explains group leader Sebastian Falk.
In the germline, piRNAs bind to Piwi argonaute proteins to repress transposable elements and maintain germline stability. Like other RNA molecules, piRNAs require post-transcriptional processing before they become fully functional, but the mechanistic details of piRNA processing are poorly understood. Using a suite of biophysical and structural tools together with in vivo studies, the researchers and their collaborators (René Ketting, Institute of Molecular Biology, Germany and Janosch Hennig, European Molecular Biology Laboratory, Germany), have characterized the architecture of the PETISCO complex and how it interacts with its effectors in the nematode C. elegans.
The researchers focused on a piRNA processing complex the Ketting lab discovered in 2019, called PETISCO. They reconstituted PETISCO from purified components, demonstrating that one element in the complex, ERH-2, serves as an interaction hub for two mutually exclusive effector proteins. Depending on which protein is bound, the complex can either fulfill one biological role or another, explaining how the PETISCO toolkit can fulfill two different functions.
The scientists now aim to further characterize the function of PETISCO in piRNA processing and to identify the nuclease that cooperates with PETISCO to process the 5’ ends of the piRNAs. The second function of PETISCO, however, still remains elusive. “We have hints that it may also be to do with RNA metabolism”, says study leader Sebastian Falk. “Since we now know the precise binding sites of the effector proteins, we will conduct targeted experiments to elucidate the evolutionary older function of PETISCO in early embryogenesis.”
Cecilia Perez-Borrajero, Nadezda Podvalnaya, Kay Holleis, Raffael Lichtenberger, Emil Karaulanov, Bernd Simon, Jérôme Basquin, Janosch Hennig, René F. Ketting, and Sebastian Falk. Structural basis of PETISCO complex assembly during piRNA biogenesis in C. elegans. Genes and Development 2021
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Evading ageing: Mitochondrial and proteostatic adaptations in oocytes
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Ubiquitin & Friends Symposium 2024
The Ubiquitin & Friends Symposium is an annual international meeting taking place in the beautiful capital of Austria, aiming to bring together scholars from various fields studying ubiquitin/Ubl biology and protein degradation in a personal, family-like atmosphere, as suggested by the name.
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Unraveling the Complexity of Crossover Regulation in C. elegans
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Title to be announced
New players in an old pathway: biology of methanogens of the TACK superphylum
Shaping morphogen gradients: from molecules to tissues and back
Title to be announced
Studying stressed cells by in situ structural biology
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Arbuscular mycorrhiza development and function
Deep homology and deep diversity: Evolving genetic toolkits for making and sensing light
The evolution of cell type identity and tissue microecology at the fetal-maternal interface
The unanticipated roles of PICIs and phages in bacterial evolution
Chemical targeting of subcellular protein localization
Origin and diversification of gut-derived organs in chordates
Job's Dilemma for the Genome: Why Bad Things Happen to Good Chromosomes
Connections between carbon and nitrogen cycling in the ocean
Understanding how the DNA-loop-extruding protein complex Condensin folds a chromatinized genome into mitotic chromosomes
DrugMap: A quantitative pan-cancer analysis of cysteine ligandability
From Roads to Rivers? Occurrence and environmental fate of tire and road wear particles and of tire-related chemicals
FENS 2024 Satellite event: Home cage behavior monitoring at the interface of animal welfare and neuroscience
Striking physiology and cell biology of (marine) environmental microorganisms
Mechanisms controlling maintenance of cohesin dependent loops
Title to be announced