iiinova — where your digital self keeps evolving

We explore the mechanism in vitro and in cells, and make the argument that this represents a new class of protein-dependent riboswitch. It's perhaps useful to think about other frameshifting signals in a similar way - especially those with reported conformational plasticity. 6/8

Interestingly, this is not a stable structure. SAXS and smFRET show that the existence of this pseudoknot is entirely dependent on the 2A protein - without it, the RNA stays as a stem-loop, unable to activate frameshifting. 5/8

Here we present the structure of the 2A-RNA complex at 1.9 Å, revealing a novel RNA pseudoknot 👇 4/8

During translation of the viral genome, ribosomes encounter an unusual blockage: a complex between a structured RNA element and the mysterious viral 2A protein. This complex is essential to activate frameshifting, but how does it work? 3/8

Many RNA viruses use programmed -1 ribosomal frameshifting as an essential gene expression strategy. Cardioviruses (e.g. EMCV, TMEV) are the absolute masters of this, causing ~85 % of ribosomes to 'slip' into the -1 reading frame. 2/8

A protein-dependent riboswitch activates ribosomal frameshifting in cardioviruses

Thrilled to share that our paper describing protein-dependent frameshifting is now out in Molecular Cell @cellpress.bsky.social. Huge congratulations to @jemmabetts.bsky.social for publishing the first research paper from her PhD 🧬🧪🥳 www.sciencedirect.com/science/arti... 1/8

sciencedirect.com

Programmed −1 ribosomal frameshifting (PRF) is a translational control mechanism used by RNA viruses to regulate the relative abundance of proteins en…

46819

Reposted by Chris H. Hill

Jamie Blaza @jnb-lab.bsky.social · 10/08/2026

Permanent academic position as a Lecturer in cryo-ET open at York. We are looking for someone to lead a research program making the most of the stunning advances occurring in cryo-ET. It's a research and teaching post but with a focus on research in the early years. jobs.york.ac.uk/vacancy/lect...

jobs.york.ac.uk

Jobs - The University of York

13838

Chris H. Hill @chillzaa.bsky.social · 11/08/2026

🚨 👇 Come and join us in York as a new lecturer (assistant professor) in cryo-ET! This is a research and teaching appointment to the York Structural Biology Laboratory (YSBL). From personal experience it's a fantastic place to start a group. Please share widely! jobs.york.ac.uk/vacancy/lect...

jobs.york.ac.uk

Jobs - The University of York

142

Chris H. Hill @chillzaa.bsky.social · 11/08/2026

Some very exciting news - cryo FIB-SEM instrumentation will soon be coming to the University of York cryo-EM facility, thanks to funding from @ukri.org BBSRC ALERT. This will enable technically demanding cryo-CLEM and in situ structural biology workflows for multiple projects ❄️🦠🧫

0123

Chris H. Hill @chillzaa.bsky.social · 06/08/2026

I'm thrilled to share that I've received a Career Development Award from the Wellcome Trust to support my laboratory @biologyatyork.bsky.social over the next eight years. Very excited for this next phase of my research journey, and looking forward to lots of twists and turns along the way! 🧬

1190

Reposted by Chris H. Hill

The Daum Lab @daumlab.bsky.social · 02/06/2026

We are looking for an enthusiastic postdoc to investigate molecular mechanisms of microsporidian infection using soft X-ray tomography, cryo FIB-SEM, and cryoET. If you are interested, do not hesitate to get in touch and check out the application link. The closing date: 21st June 2026.

2158

Chris H. Hill @chillzaa.bsky.social · 16/05/2026

We just had our second -80 freezer failure in four years... On a Friday evening of course. All samples transferred safely, thanks to the amazing dedication of my team. Eppendorf CryoCube is disappointing in every possible way - it's neither a cube, nor does it stay cold.

3163

Chris H. Hill @chillzaa.bsky.social · 30/04/2026

Abstract submission for @biochemsoc.bsky.social Translation UK 2026 closes at 🚨MIDNIGHT 🚨 tonight! Please join us in Leeds for this fantastic meeting 👇 www.eventsforce.net/biochemsoc/f...

046

Chris H. Hill @chillzaa.bsky.social · 20/04/2026

Two weeks left for abstract submission - please do register; it's a great UK meeting, and lots of opportunities for ECRs to share their work 👇

033

Chris H. Hill @chillzaa.bsky.social · 17/04/2026

The @biochemsoc.bsky.social Translation UK 2026 meeting will be at @universityofleeds.bsky.social from 30th June - 2nd July. Fantastic keynote speakers including @jbquerido.bsky.social, @nickywhiffin.bsky.social, Nicolas Locker Register and submit your abstract here: tinyurl.com/muy5kvax

0135

Reposted by Chris H. Hill

Exciting Instruments @ei-science.bsky.social · 10/04/2026

🤔 How do #proteins reshape RNA dynamics? Static structures tell only half the story. Using smFRET on the EI-FLEX, the @chillzaa.bsky.social lab at @yorkuniversity.bsky.social mapped viral protein–dependent RNA pseudoknot formation - revealing it as a binary, protein-triggered event > buff.ly/IVQYK72

031

Chris H. Hill @chillzaa.bsky.social · 06/01/2026

🚨Last chance to apply for two PhD projects in my lab, applying structural biology and single molecule biophysics to investigate gene expression in RNA viruses: www.findaphd.com/phds/?Keywor...

findaphd.com

01010

Reposted by Chris H. Hill

Chris H. Hill @chillzaa.bsky.social · 13/11/2025

🚨Attention prospective PhD students🚨 Are you interested in molecular mechanisms, RNA viruses, structural biology or biophysics? 🧬🦠🧪 We have THREE fully-funded PhD projects available for October 2026 entry: www.findaphd.com/phds/?Keywor... Please share/repost, and get in touch if you're interested

findaphd.com

chris hill PhD Projects, Programmes & Scholarships - 3 PhDs Listed

FindAPhD. Search Funded PhD Projects, Programmes & Scholarships in chris hill. Search for PhD funding, scholarships & studentships in the UK, Europe and around the world.

01213

Chris H. Hill @chillzaa.bsky.social · 13/11/2025

findaphd.com

chris hill PhD Projects, Programmes & Scholarships - 3 PhDs Listed

FindAPhD. Search Funded PhD Projects, Programmes & Scholarships in chris hill. Search for PhD funding, scholarships & studentships in the UK, Europe and around the world.

01213

This was a fantastic collaboration with the groups of @valerialulla.bsky.social @campathology.bsky.social and Trevor Sweeney @pirbrightinst.bsky.social. Thanks also to superb colleagues and facilities @biologyatyork.bsky.social, YSBL, @ybri-uoy.bsky.social and @diamondlightsource.bsky.social

040

The mechanism of ribosomal recruitment during translation initiation on Type 2 IRESs

These findings are similar to recent work on the EMCV Type 2 IRES — see e.g. www.biorxiv.org/content/10.1...; www.biorxiv.org/content/10.1... — and suggest that common structural motifs and mechanisms may exist within highly divergent picornavirus IRES sequences

biorxiv.org

The encephalomyocarditis virus (EMCV) IRES and other Type 2 IRESs comprise domains H-L and specifically interact with eIF4G/eIF4A through their essential JK domain. However, the JK domain is not suffi...

131

To validate our structures, in collaboration with @valerialulla.bsky.social @campathology.bsky.social , we carry out targeted disruption of domain IVc in related enterovirus CVA13. These mutations are highly detrimental to viral translation and replication in both HeLa and HIEC6 cell lines

IRES domain IVc contacts uS19 and uS13 on the 'head' of the small ribosomal subunit, whilst the conserved apical GNRA tetraloop interacts directly with the initiator tRNA

In our preprint, we reconstitute human translation initiation on a model poliovirus IRES and examine 48S complexes by cryo-EM. Our structures reveal a network of interaction between IRES domain IVc and the translation machinery during start-codon recognition (closed 48S complexes)

140

Enteroviruses use an internal ribosome entry site (IRES) within the 5′ UTR to recruit the translation machinery. Type 1 IRESs are large (~450 nt), flexible RNAs that require numerous eIFs and the host factor PCBP2 — making them very challenging structural targets

Structural and mechanistic insights into translation initiation on the enterovirus Type 1 IRES

Enteroviruses cause over a billion infections each year, but the details of how their genomes capture host ribosomes have remained elusive. I'm pleased to share a new preprint from Miguel in our group, providing some new insights into this problem: www.biorxiv.org/content/10.1...

biorxiv.org

Enteroviruses are a widespread and diverse set of pathogens responsible for over ~1 billion human infections annually. Upon cell entry, translation of the virus genome is mediated by an internal ribos...

1259

Reposted by Chris H. Hill

Oli Clarke @olibclarke.bsky.social · 13/09/2025

This one is a bit of a departure from the usual and definitely a work in progress! We found that by using ab initio reconstruction at very high res, in very small steps, we could crack some small structures that had eluded us - e.g. 39kDa iPKAc (EMPIAR-10252), below. Read on for details... 1/x

2026782

Chris H. Hill @chillzaa.bsky.social · 30/07/2025

Ever struggled with low PNK efficiency on a highly structured piece of RNA? Sarah solved this problem by using a DNA scaffold to make the 5' end more accessible, improving the efficiency of end labelling. This enabled us to make smFRET measurements on the SARS-CoV-2 pseudoknot 🧬🔴🟢

050

Chris H. Hill @chillzaa.bsky.social · 21/07/2025

Thanks Ahmad, it was great to see you again too :)

010

Thanks also to the superb facilities at @biologyatyork.bsky.social, YSBL and @ybri-uoy.bsky.social, light source access @diamondlightsource.bsky.social and DESY, and to our funders, including @wellcometrust.bsky.social @royalsociety.org, BBSRC, EPSRC, DiMEN DTP and @thelisterinstitute.bsky.social

We explore the mechanism in detail, and make the argument that this represents a new class of protein-dependent riboswitch. It's perhaps useful to think about other frameshifting signals in a similar way - especially those with reported conformational plasticity.

100

Amazingly, this is not a stable structure. We use SAXS and single molecule FRET to show that the existence of this pseudoknot is entirely dependent on the 2A protein - without it, the RNA stays as a stem-loop, unable to activate frameshifting.

Here we present the structure of the 2A-RNA complex at 1.9 Å, revealing a novel RNA pseudoknot 👇

During virus genome translation, ribosomes encounter an unusual blockage: a complex between a structured RNA element and the mysterious viral 2A protein. This complex is essential to activate frameshifting, but how does it work?

100