SFB 80: RNA-DECO
Decorating RNA
for a purpose

To date, more than 150 natural RNA modifications have been identified. However, the function and interplay among RNA modifications remains enigmatic.
The Vilardo lab investigates RNA modifications in tRNAs, the key adaptor molecules between gene expression and protein translation. We use biochemistry, genome editing by Crispr/Cas9, and Next Generation Sequencing to investigate tRNA modifications and the enzymatic pathways responsible for modifications.
As part of the special research focus program RNA-Deco, we collaborate within a network of top RNA research laboratories across Austria.

If you are a highly motivated student in biology, biotechnology or similar subjects, and are interested to join our group at the Center for Anatomy and Cell Biology of the Medical University of Vienna, please send curriculum vitae,
motivation letter and a recommendation letter to:
elisa.vilardo@meduniwien.ac.at

An EU-funded Ph.D. position is available in the lab of Michael Jantsch. The international training network (ITN) consists of a multinational team studying RNA modifications in a multidisciplinary approach. Secondments allow diverse training and research experiences at a competitive salary including family allowance.
The lab of Michael Jantsch studies adenosine deamination in mice which is one of the most abundant RNA modifications in mammals. Deamination of adenosines (A) leads to the formation of inosines (I). Inosines are interpreted as guanosines by most cellular machineries, including translation.
A to I editing is mediated by two enzymes, ADAR1 or ADAR2. While ADAR2 is mainly responsible for editing events that alter the coding of mRNAs or the function of small RNAs, ADAR1 acts as an antiviral protein. Interestingly, loss of ADAR1 leads to elevated interferon signaling and upregulation of the antiviral signals.
It will be the aim of this Ph.D. project to decipher the signals that trigger antiviral responses and to determine how the introduction of inosines prevents antiviral signaling (Fig 1).

Figure 1: Sensing of dsRNA by antiviral immune proteins. In the absence of A to I editing, dsRNA activates antiviral signaling by recruiting and activating the MDA5-MAVS signaling pathways. In the presence of inosines this pathway is suppressed. Currently, the underlying mechanisms are not well understood.

The Division of Cell & Developmental Biology provides a stimulating atmosphere for RNA research with five research groups working on RNA modifications. The team is tightly linked to other Austrian RNA researchers via an RNA research network. The Division of Cell & Developmental Biology is located near the center of historic Vienna.

Interested candidates, please send their application including a curriculum vitae, a letter of motivation and two contacts for references to
Michael.Jantsch@meduniwien.ac.at under the reference “ROPES”
until March 30th 2021
For further information please visit:
ROPES: https://cordis.europa.eu/project/id/956810/de
https://www.rna-deco.org/
https://anatomieundzellbiologie.meduniwien.ac.at/group-jantsch

Background: Adenosine deaminases acting on RNA deaminate adenosines to inosines in structured regions of RNAs. The RNA-editing process occurs in millions of sites in the human transcriptome. As inosines are interpreted as guanosines during translation, this RNA-editing process can alter codons and therefore lead to the formation of proteins that are not encoded in the genome. A prominent adenosine to inosine deamination event is found in the mRNA encoding filamin A, an abundant actin crosslinking protein that links the cellular cortex and transmembrane proteins with the cytoskeleton. Changes in the editing pattern of the filamin A mRNA lead to the expression of altered filamin A which causes high blood pressure but also causes gastrointestinal inflammatory disorders. To understand the molecular consequences of the editing-induced amino acid exchange, the affected domain will be studied by structural and biophysical means.

Thesis description: We are looking for a highly motivated and dedicated student to use a combination of structural and molecular biophysics approaches to investigate the molecular consequences of RNA-editing of filamin A. The successful candidate will have the opportunity to (i) express and purify native and “edited” variants and perform a comparative molecular biophysics analysis (ii) X-ray crystallography to determine their structures at high resolution (iii) use biochemical and biophysical methods to validate the mechanistic model.

Requirements: background in biochemistry or molecular biology, studies of Molecular Biology, Biochemistry, Chemistry, Cell Biology or related fields.

Application Details: Interested students, please send
• A cover letter
• Your CV
• Contact details of two referees
To Michael Jantsch <michael.jantsch@meduniwien.ac.at> and Kristina Djinovic-Carugo <Kristina.Djinovic@univie.ac.at>
Duration of thesis: 12 months, salary: 440 € per month. Beginning: immediately.

Further Information:
https://anatomieundzellbiologie.meduniwien.ac.at/abteilungen-wissenschaft-forschung/abteilung-fuer-zell-u-entwicklungsbiologie/epigenetics-and-rna-biology/group-jantsch/
https://www.maxperutzlabs.ac.at/research/research-groups/djinovic

Relevant Publications:
https://doi.org/10.15252/embj.201694813
https://doi.org/10.1080/15476286.2018.1480252