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

Group Leader

PhD Student

PhD Student

PhD Student

PhD Student

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

2021

Structural and molecular basis for Cardiovirus 2A protein as a viral gene expression switch

Hill CH, Pekarek L, Napthine S, Kibe A, Firth AE, Graham SC, Caliskan N, Brierley I (2021)

Nature Communications 12 (1): 7166

Investigating molecular mechanisms of 2A-stimulated ribosomal pausing and frameshifting in Theilovirus

Hill CH, Cook GM, Napthine S, Kibe A, Brown K, Caliskan N, Firth AE, Graham SC, Brierley I (2021)

Nucleic Acids Research 49 (20): 11938-11958

The short isoform of the host antiviral protein ZAP acts as an inhibitor of SARS-CoV-2 programmed ribosomal frameshifting

Zimmer MM, Kibe A, Rand U, Pekarek L, Ye L, Buck S, Smyth RP, Cicin-Sain L, Caliskan N (2021)

Nature Communications 12 (1): 7193

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

Jun Prof Neva Caliskan

Recoding Mechanisms in Infections

Our research and approach

Team members