Jun Prof Neva Caliskan
Recoding Mechanisms in Infections
The research group lead by Neva Caliskan investigates functions and dynamics of RNA molecules in non-canonical translation events, which can affect the interplay between the host and pathogen during infection. Ultimately, they seek to illuminate therapeutic RNA-protein complexes as novel targets to combat infections.
Our research and approach
Viruses and cellular genes encode RNAs that can be read in alternative ways during translation, which is called recoding. However, how exactly recoding is regulated by host encoded factors remains elusive. Here, a detailed understanding of recoding and its regulation can open doors for the development of novel RNA-based therapeutic interventions to combat infections.
Neva Caliskan’s group investigates the functions and dynamics of RNA molecules and their interplay with trans-acting factors involved in recoding events. They work with several viruses known to depend on recoding strategies for replication including corona and retroviruses, and develop methods to investigate RNA complexes and translation in unprecedented detail.
The group employs a highly interdisciplinary toolset including RNA-antisense purification and mass spectrometry to identify RNA-interaction partners, and cellular assays to investigate molecular details. Ensemble and single molecule assays such as optical tweezers are key to study the dynamics of RNA complexes. Ultimately, they seek to understand how RNA-structure elements act in concert with other factors in the cell to modulate the way mRNA messages are read by ribosomes during infections to advance RNA-based therapeutics.
Team members
Jun Prof Neva Caliskan
Group Leader
Anuja Kibe
PhD Student
Lukáš Pekárek
PhD Student
Matthias Zimmer
PhD Student
Ricarda Riegger
PhD Student
Tatyana Koch
Technical Assistant
Research projects
Many bacterial and viral pathogens and also their eukaryotic host cells employ non-canonical translation strategies in order to express hidden genes from alternative open reading frames (Caliskan et al., 2015). RNA is a versatile molecule that acts as a key regulator of non-canonical translation events. RNA can exist in various shapes and interact with other regulatory elements such as ncRNAs, small molecules and proteins to alter the meaning of the message encoded in the primary sequence of the mRNA. How RNA structure and regulatory elements drive alternative translation events is currently not fully understood. In addition, it is largely unclear to what extend these translation events are used by the pathogen and the host cell during infections. We use cutting-edge RNA analytics, such as ribosome profiling and deep sequencing combined with single molecule and computational tools to understand dynamics of translation and the functions of RNA regulators during infections. Ultimately, we want to better understand the interplay between the host’s and pathogen’s gene expression and harness our knowledge to develop novel therapeutic strategies to combat infectious diseases.
Publications
2020
Structural studies of Cardiovirus 2A protein reveal the molecular basis for RNA recognition and translational control
Hill CH, Napthine S, Pekarek L, Kibe A, Firth AE, Graham SC, Caliskan N, Brierley I (2020)
Preprint
Structural and molecular basis for protein-stimulated ribosomal frameshifting in Theiler’s murine encephalomyelitis virus
Hill CH, Cook G, Napthine S, Kibe A, Brown K, Caliskan N, Firth AE, Graham SC, Brierley I (2020)
Preprint
The SARS-CoV-2 RNA-protein interactome in infected human cells
Schmidt N, Lareau CA, Keshishian H, Ganskih S, Schneider C, Hennig T, Melanson R, Werner S, Wei Y, Zimmer M, …, Bodem J, Munschauer M (2020)
Nature Microbiology 6 (3): 339-353
2019
Thermodynamic control of -1 programmed ribosomal frameshifting
Bock LV, Caliskan N, Korniy N, Peske F, Rodnina MV, Grubmüller H (2019)
Nature Communications 10: 4598
2018
Small synthetic molecule-stabilized RNA pseudoknot as an activator for -1 ribosomal frameshifting
Matsumoto S, Caliskan N, Rodnina MV, Murata A, Nakatani K (2018)
Nucleic Acids Research 46 (16): 8079-8089
2017
Conditional Switch between Frameshifting Regimes upon Translation of dnaX mRNA
Caliskan N, Wohlgemuth I, Korniy N, Pearson M, Peske F, Rodnina MV (2017)
Molecular Cell 66 (4): 558-567
2016
Choreography of molecular movements during ribosome progression along mRNA
Belardinelli R, Sharma H, Caliskan N, Cunha CE, Peske F, Wintermeyer W, Rodnina MV (2016)
Nature Structural & Molecular Biology 23 (4): 342-8
2015
Changed in translation: mRNA recoding by -1 programmed ribosomal frameshifting
Caliskan N, Peske F, Rodnina MV (2015)
Trends in Biochemical Sciences 40 (5): 265-74
2014
Programmed -1 frameshifting by kinetic partitioning during impeded translocation
Caliskan N, Katunin VI, Belardinelli R, Peske F, Rodnina MV (2014)
Cell 157 (7): 1619-31