Faraz Mardakheh

Come work with Ben Berks FRS in Oxford
2 x PDRA posts: Molecular Analysis of Bacterial Outer Membrane Protein Biogenesis

2 complementary projects investigating bacterial outer membrane protein biogenesis. Building on our recent work (Nature (2015) 647: 479-487)

my.corehr.com/pls/uoxrecru...

UBA6 specificity for ubiquitin E2 conjugating enzymes reveals a priority mechanism of BIRC6 Nature Structural & Molecular Biology - Riechmann et al. uncover structural features governing ubiquitin transfer from ubiquitin-activating E1 enzymes UBA1 and UBA6 to specific E2...

Excited to share our work into ubiquitin E1-E2 specificity mechanisms. CryoEM visualising #ubiquitin transfer,biochemistry,evolution @labhofmann.bsky.social & tissue expression analyses @psarkies.bsky.social Big thanks to the team,reviewers & handling editor @dimitristypas.bsky.social rdcu.be/eTRdR

Thanks Vardhman!

Thanks Dan!

Thanks Phil!

Finally, a big thank you to our funders for their support @ukri.org, and to @natcomms.nature.com for an excellent peer review experience!

@oxfordbiochemistry.bsky.social @kingscollegelondon.bsky.social
@qmbci.bsky.social

Also a massive thank you to all our amazing collaborators @genophoria.bsky.social, Geof Kelly, Laura Masino, and all the other listed authors for their amazing support. This work would have not been possible without your contributions. 9/10

This study was a massive team effort between my lab (www.mardakhehlab.info) and the lab of Sasi Conte (www.kcl.ac.uk/research/the...). Big kudos goes to the joint first authors Federica Capraro and Giancarlo Abis for their incredible effort🍾 8/10.
#teamwork

Big-picture takeaway: IDRs can enhance the RNA binding specificity of their nearby structured domains and this is functionally important. Crucially, the majority of disease causing mutations in RBPs seem to occur in IDRs, suggesting that these fine-tuning activities are likely disease-relevant! 7/10

In other words, the IDR acts less like a “sticky binding patch", and more like a specificity gate for the structured domain. But does all this matter? The answer is yes! We show that the IDR-mediated RNA-binding selectivity is critical for LARP6 promotion of cancer cell viability and invasion! 6/10

But what is the mechanism? Using NMR and SAXS analysis, we show that the N-term. IDR restricts the conformational flexibility of its adjacent La-module, adds auxiliary contacts with the substrate RNAs, as well as gating the access of unwanted RNA to the La-module 5/10.

But IDRs still matter! We found that deleting the N-term. IDR broadened LARP6 RNA footprints, suggesting a role in promoting the RNA-binding selectivity of the La-module. Critically, these iCLIP observations could be reproduced in vitro, suggesting this is an intrinsic property of the IDR! 4/10

But what RNA sequences do these IDRs bind to? To address this, with performed mutagenesis + iCLIP. Surprisingly, we found that IDRs on their own do not significantly bind to any RNA, and the La-module is absolutely required for the RNA binding activity of LARP6 in cells. 3/10

To tackle this question, we focused on LARP6, a conserved RBP with a diverse RNA-binding repertoire, which contains an structured RNA binding region (La-module) flanked by 2 IDRs. Using Mass spec–based RNA interaction mapping, we found direct RNA contacts in the La-module & the flanking IDRs. 2/10.

🎉Proud to present our latest paper, out now in Nature Communications: www.nature.com/articles/s41...

RNA Binding Proteins (RBPs) are often full of intrinsically disordered regions (IDRs), but what these regions do during RNA recognition is often unclear. 1/10
#RNA #IDR #RBP

UKRI CEO updates the research community on areas of uncertainty Following an open letter of 1 February, Sir Ian Chapman responds to feedback and provides an update.

For those following the developments of research funding in the UK, here is another letter from Ian Chapman about UKRI:
www.ukri.org/news/ukri-ce...

A massive well done to our recently graduated PhD student and new postdoc @emiliealard.bsky.social for winning the RNA UK 2026 best talk prize🏆 👏👏👏#ProudPI #RNAUK2026

Join us;
We have an opening for a BBSRC-funded 3-year postdoc position to investigate the mechanisms of mRNA-specific translational regulation of the innate immune system.

#Postdoc #RNA #RBP #MolecularBiology #Virology #RNASky #AcademicJobs

hrwebapp.qub.ac.uk/tlive_webrec...

RNA in physiology and disease | Genetics Society Meeting background RNA molecules are at the heart of normal physiological processes, and their dysregulation can drive a wide range of human diseases. This international meeting will bring together wo...

Have a look at this fantastic meeting and save the date!

The “RNA in Physiology and Disease” conference, hosted by @gensocuk.bsky.social, will take place 7–9 September 2026 in Newcastle, UK.

genetics.org.uk/events/rna-i...

Pre-assembly of biomolecular condensate seeds drives RSV replication Nature - Viral ribonucleoprotein–viral protein networks form pre-replication centres that nucleate viral factories and drive respiratory syncytial virus replication.

Now out in Nature! We visualize infection of the RNA virus RSV in real-time with single-vRNP resolution to understand how RSV establishes viral factories, biomolecular condensates that act as sites of viral replication. A huge collaborative effort led by Dhanushika Ratnayake!

rdcu.be/e1bBW

Leveraging what you learned from this graph ;)

Image screening is going to fail. We need audit trails for data provenance.

We’ll soon be advertising a postdoc position (3 years) to study how mRNA-specific translational regulation shapes the innate immune system, in collaboration with @alf-castello.bsky.social. The formal ad will be out soon but get in touch if you’d like an informal chat! #RNASky

mRNA 3′ UTRs direct microRNA degradation to participate in imprinted gene networks and regulate growth MicroRNAs direct downregulation of target mRNAs. Sometimes, however, this regulatory paradigm inverts, and a target RNA triggers the degradation of a microRNA. This target-directed microRNA degradatio...

Check out the latest work from our lab, led by Daniel Lin and Lara Elcavage: www.biorxiv.org/content/10.1... (1/3)

🚨 #RNAsky 🚨

Single Nucleotide Resolution 4sU Sequencing (SNU-Seq) reveals the transcriptional responsiveness of an epigenetically primed human genome Genomes are pervasively transcribed, leading to stable and unstable transcripts that influence 3-dimensional genome organisation and gene regulation. High sensitivity and nucleotide resolution are req...

🧬 New preprint!
SNU-Seq maps nascent transcription at single-nucleotide resolution using 4sU labeling.
Together with sf4sU-Seq, it shows how epigenetically primed chromatin rapidly activates transcription after IFN-γ.
📄 doi.org/10.1101/2021...
#SNUSeq #RNAseq

Enhanced hybridization-proximity labeling discovers protein interactomes of single RNA molecules - Nature Communications Systematic discovery of proteins interacting with low-abundance RNAs is challenging. Here, the authors develop an enhanced HyPro technology to identify proteins associated with compact RNA compartment...

Our paper describing enhanced hybridization-proximity labeling technology is finally out! Enhanced HyPro can identify proteins associated with small RNA compartments and even some individual transcripts, such as pathological C9orf72 transcripts: www.nature.com/articles/s41...

John Gurdon obituary: Biologist who made cloning possible He showed that specialized cells retain the genes to form an organism.

new out in Nature www.nature.com/articles/d41...

We are recuiting two new Associate Professors here in Oxford Biochemistry. Come join us! Reach out to me if you have any questions. Please repost! tinyurl.com/mr3m7bd3

A cGAS-mediated mechanism in naked mole-rats potentiates DNA repair and delays aging Efficient DNA repair might make possible the longevity of naked mole-rats. However, whether they have distinctive mechanisms to optimize functions of DNA repair suppressors is unclear. We find that na...

The enzyme cGAS senses DNA damage, but in humans and mice it inhibits a DNA repair pathway (homologous recombination), which reduces genome stability. In naked mole-rats, altering 4 amino acids in cGAS changes its role: instead of hampering repair, it boosts it.

www.science.org/doi/10.1126/...