Molecular mechanisms in RNA Biology
The genetic makeup of an organism is stored in DNA, but it is RNA that brings this code to life. RNAs exist in many forms and performs countless functions in the cell, from carrying genetic information to ribosomes to produce proteins, to guiding the modification of other RNAs or regulating the transcriptome. The doc.funds program brings together Viennese scientists to tackle different aspects of RNA biology with the goal of educating the next generation of RNA biologists. “The power of this network relies in sharing knowledge, ideas and technologies to provide the best education for students interested in RNA biology”, says speaker and Max Perutz Labs group leader Javier Martinez. Besides scientific training, students will benefit from seminars, retreats, and training in soft skills, including different aspects of science communication. “Students will be able to expand their views through exchanges with other participating labs and by conducting internships in biotech companies, thereby providing career perspectives for our students”, says deputy speaker Sebastian Falk. The doc.funds program offers 10 fully funded PhD positions together with a budget for educational activities. The recruitment will start in spring 2023 through the International Vienna BioCenter PhD program.
Stefan Ameres, Sebastian Falk, Boris Görke, Elif Karagöz, Javier Martinez, Isa Moll (Max Perutz Labs), Julius Brennecke (IMBA), Clemens Plaschka (IMP), Matthias Schäfer & Elisa Vilardo (Medical University of Vienna)
Joanna Jachowicz (IMBA), Silvia Ramundo (GMI)
TRIM52 – an immunity gene with non-immunity roles
Upon infection with pathogens, cells trigger the production of signaling molecules called interferons that upregulate genes involved in the innate immune systems. Many members of the tripartite motif-containing (TRIM) family of proteins are known to be expressed in response to interferon signaling. They play an important role in resistance to pathogens, particularly infection by lentiviruses. One family member, however, has puzzled the Versteeg lab for some time. Unlike other TRIM proteins, TRIM52 exhibits no antiviral activity. While TRIM52 appears to be essential for cellular fitness and survival, it is not conserved across mammals and is very rapidly turned over in the cell. “In our project we will use an in vitro biochemical reconstitution approach, genetic screens and interaction screens to understand more about the functions and degradation mechanisms of this protein”, explains Gijs Versteeg.
Keeping jumping genes in check
Most genes are found at specific, fixed positions on chromosomes, but not all. So-called transposons, or jumping genes, can change their location, which carries the risk of introducing pathological mutations into the genome. Piwi-interacting RNAs (piRNAs) are essential to repress transposable elements in the animal germline. In the nematode worm C. elegans, piRNA biogenesis requires a protein complex called PETISCO. In 2021, the Falk lab and their collaborators in the lab of René Ketting at the IMB Mainz have, for the first time, characterized the architecture of the PETISCO complex, including how it interacts with its effectors. “We were able to answer a lot of questions regarding PETISCO, but many more emerged”, says Sebastian Falk. “With the joint weave grant, we will be able to continue our fruitful collaboration. We will use cell biology, genetics, genomics, and structural biochemistry to focus on how piRNA precursors are correctly processed in the cell to mediate the downstream repression of transposons”.