Eric Miska
Associate group leaderResearch summary
Non-coding RNA and genome dynamics
What does non-coding RNA do in development and disease? Most of the RNA transcribed from the DNA in our genome is not translated into protein but instead has direct functions in regulating biological processes. This paradigm shift in nucleic acid biology has been supported by technical advances in high-throughput sequencing, molecular genetics and computational biology, which can be combined with more traditional biochemical analyses.
Many species and roles of non-coding RNA have been identified. Our goal is to understand how non-coding RNAs regulate development, physiology and disease. We are exploring microRNA in the pathology of cancer and other diseases, RNA interference in viral immunity, Piwi- interacting RNA in germline development and genome integrity, and endogenous small interfering RNA in epigenetic inheritance – where we predict a big impact in understanding human health.
Our model organisms are the nematode worm, the cichlid fishes of the Rift Lakes of East Africa, mouse, and human cell culture. More recently we have developed a technology to assess RNA structure and RNA–RNA interactions in living systems. We used this to uncover unexpected biology for the Zika virus, and key regulatory mechanisms for SARS- CoV-2.
The Zika virus genomic structure inside human cells. The Zika virus genome adopts alternating structures as the 5′ cyclization sequence (CS) participates in interaction with host microRNA miR-21 (top), capsid translation (right), and genome cyclization (left).
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Selected publications
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Burton NO et al. (2021) Intergenerational adaptations to stress are evolutionarily conserved, stress-specific, and have deleterious trade-offs. eLife 10:e73425. DOI: 10.7554/eLife.73425.
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Vernaz G et al. (2021) Mapping epigenetic divergence in the massive radiation of Lake Malawi cichlid fishes. Nat Commun 12(1):5870. DOI: 10.1038/s41467-021-26166-2.
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Gapp K et al. (2021) Single paternal dexamethasone challenge programs offspring metabolism and reveals multiple candidates in RNA-mediated inheritance. iScience 24(8):102870. DOI: 10.1016/j.isci.2021.102870.
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Miska EA & Rechavi O (2021) Can brain activity transmit transgenerationally? Curr Top Dev Biol 144:1-18. DOI: 10.1016/bs.ctdb.2021.03.001.
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Berkyurek AC et al. (2021) The RNA polymerase II subunit RPB-9 recruits the integrator complex to terminate Caenorhabditis elegans piRNA transcription. EMBO J 40:e105565. DOI: 10.15252/embj.2020105565.
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Navarro IC et al. (2021) Translational adaptation to heat stress is mediated by RNA 5-methylcytosine in Caenorhabditis elegans. EMBO J 40:e105496. DOI: 10.15252/embj.2020105496.
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Ziv O et al. (2020) The Short- and Long-Range RNA–RNA Interactome of SARS-CoV-2. Mol Cell 80: 1067–1077.e5. DOI: 10.1016/j.molcel.2020.11.004.
Biography
Prof Eric Miska PhD
Associate Group Leader; Head of Department of Biochemistry; Wellcome Senior Investigator, Cancer Research UK Senior Research Fellow, Herchel Smith Professor of Molecular Genetics, Associate Faculty Member of the Wellcome Sanger Institute