Gopal Jayaraj

Proteotoxic stress response drives T cell exhaustion and immune evasion - Nature A proteotoxic stress response specific to exhausted T cells, governed by AKT signaling and accompanied by increased protein translation, represents a mechanistic vulnerability and a new therapeutic target to improve cancer immunotherapies.

www.nature.com/articles/s41...

The human ribosome modulates multidomain protein biogenesis by delaying cotranslational domain docking - Nature Structural & Molecular Biology By studying dynamic folding intermediates on the human ribosome, Pellowe et al. show that newly made domains help each other to fold but do not stably interact until synthesis is complete, avoiding in...

Our article on human multidomain protein biogenesis is now published in @natsmb.nature.com
www.nature.com/articles/s41...

Apply by Oct 15 - please spread the word!

Why are α-synuclein aggregates in Parkinson’s disease (PD) toxic at the cell biological level?

Our new study shows that α-syn fibrils hijack the ESCRT membrane repair system, triggering a feedback loop that worsens aggregation.

You can find it at: authors.elsevier.com/sd/article/S...

Lysosomal RNA profiling reveals targeting of specific types of RNAs for degradation Autophagy targets a wide variety of substrates for degradation within lysosomes. While lysosomes are known to possess RNase activity, the role of lysosomal RNA degradation in post-transcriptional gene...

I am excited to share my graduate work in the Sabatini and @bartellab.bsky.social labs. Since their discovery, we have known lysosomes possess RNase activity; however, their substrates were not known. Surprisingly we find specific RNAs are targeted for degradation! www.biorxiv.org/content/10.1...

Glad to share the final version of our story about the UBR4 complex, an E4 ligase protein quality control hub @science.org. Now with more cryo-EM structures and a deeper dive into substrate recognition, especially escaped mitochondrial proteins @clausenlab.bsky.social www.science.org/doi/10.1126/...

A split-site E3 ligase mechanism enables ZNFX1 to ubiquitinate and cluster single-stranded RNA into ubiquitin-coated nucleoprotein particles Grabarczyk et al. show the structure and mechanism of a non-canonical ubiquitin ligase, which is activated through nucleic-acid-induced oligomerization and is critical for cell survival during immune ...

Happy to share our work on the structure and function of the unusual E3 ligase ZNFX1 @cp-cell.bsky.social. It uses a nucleic acid-activated transthiolation mechanism, ubiquitinating and clustering RNA to protect cells in an immune response. @clausenlab.bsky.social
www.cell.com/cell/fulltex...

LOV-BirA, light regulated biotin ligase, engineered by Song-Yi Lee

www.sciencedirect.com/science/arti...

Excited to see this work published online at @cp-cell.bsky.social today!

www.cell.com/cell/fulltex...

Complex II assembly drives metabolic adaptation to OXPHOS dysfunction Succinate dehydrogenase assembly dynamics maintains metabolic homeostasis during mitochondrial oxidative stress.

Complex II assembly drives metabolic adaptation to OXPHOS dysfunction | Science Advances www.science.org/doi/10.1126/...

Structural analyses define the molecular basis of clusterin chaperone function Nature Structural & Molecular Biology - The authors reveal a three-domain architecture of glycoprotein clusterin and show that the hydrophobic tails are crucial for clusterin’s functions...

Curious about the structure and functional analysis of one of the most abundant and enigmatic extracellular #chaperones and one of the highest genetic risk factor for developing late onset #Alzheimer’s disease? Check out our paper on Clusterin/ApoJ!
#proteostasis #apolipoprotein
rdcu.be/ezRLv

#proteostasis mRNA 3′UTRs chaperone intrinsically disordered regions to control protein activity
www.biorxiv.org/content/10.1...

Probing condensate microenvironments with a micropeptide killswitch - Nature Targeting a non-natural micropeptide ‘killswitch’ to several biomolecular condensates altered condensate compositions and revealed condensate functions in human cells

www.nature.com/articles/s41...

New from our lab @crick.ac.uk, in collaboration with the Enchev and Bukau labs.
By studying a protein that is difficult to fold, we discover fascinating new mechanisms by which the ribosome supports protein biogenesis.
www.biorxiv.org/content/10.1...

HCR-Proxy resolves site-specific proximal RNA proteomes at subcompartmental nanoscale resolution The spatial organisation of RNA condensates is fundamental for understanding of basic cellular functions, but may also provide pivotal insights into diseases. One of the major challenges to understand...

www.biorxiv.org/content/10.1...

Check this from the Modic lab

Translational activity of 80S monosomes varies dramatically across different tissues Abstract. Translational regulation at the stage of initiation can impact the number of ribosomes translating each mRNA molecule. However, the translational

Delighted to share paper on translational activity of 80S monosomes across different tissues in 🪰 in @narjournal.bsky.social thanks to fabulous team Albert Blandy Tayah Hopes Elton Vasconcelos @amy-turner96.bsky.social Bulat Fatkhullin Michaela Agapiou Juan Fontana academic.oup.com/nar/article/...

The nascent polypeptide-associated complex (NAC) as regulatory hub on ribosomes The correct synthesis of new proteins is essential for maintaining a functional proteome and cell viability. This process is tightly regulated, with ribosomes and associated protein biogenesis factors...

doi.org/10.1515/hsz-...

I am super happy to share this review as my first post on Bluesky. After submitting my PhD thesis at the start of the year, my PI Elke Deuerling suggested to write this review with her, covering many of the findings of my thesis. I am excited to see it published today!

A subcellular map of translational machinery composition and regulation at the single-molecule level Millions of ribosomes are packed within mammalian cells, yet we lack tools to visualize them in toto and characterize their subcellular composition. In this study, we present ribosome expansion micros...

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

Mitochondria serve as a Holdout Compartment for Aggregation-Prone Proteins hindering Efficient Ubiquitin-Dependent Degradation The accumulation of protein aggregates has been causatively linked to the pathogenesis of neurodegenerative diseases. In this study, we have conducted a genome-wide CRISPR-Cas9 screen to identify cell...

Mitochondria a safe haven for aggregation-prone proteins? #neurodegeneration. #Parkinson. Find our latest manuscript in @biorxivpreprint.bsky.social www.biorxiv.org/content/10.1...

The ribosome as a platform to coordinate mRNA decay Abstract. Messenger RNA (mRNA) homeostasis is a critical aspect of cellular function, involving the dynamic interplay between transcription and decay proce

Exicted to share our latest review in @narjournal.bsky.social on how the ribosome coordinates mRNA decay with a focus on structural advances in the field.

#ribosome #mRNAdecay #translation

Long-term imaging of individual ribosomes reveals ribosome cooperativity in mRNA translation Ribosomes cooperate through transient collisions to ensure efficient translation.

www.cell.com/cell/fulltex...

C-terminal amides mark proteins for degradation via SCF–FBXO31 - Nature SCF–FBXO31 scans proteins for C-terminal amidation and marks them for subsequent proteasomal degradation.

🎉Super excited to share our story on how the substrate receptor FBXO31 functions as a quality control factor by recognizing amides. This has been an amazing collaboration between Bode lab and @jcornlab.bsky.social. Special shutout goes to @matthiasmuhar.bsky.social www.nature.com/articles/s41...

Mechanism of chaperone recruitment and retention on mitochondrial precursors Nearly all mitochondrial proteins are imported into mitochondria from the cytosol. How nascent mitochondrial precursors acquire and sustain import-competence in the cytosol under normal and stress con...

www.biorxiv.org/content/10.1...

Postdoctoral Fellow - Balchin Lab Salary for this Role: From £43,210 with benefits, subject to skills and experience Job Title: Postdoctoral Fellow - Balchin Lab Reports to: David Balchin Closing Date: 28/Feb/2025 23.59 GMT Job Descri...

We're hiring a postdoc!
Applications from any nationality welcome.
Projects around protein folding in cells, ribosomes, chaperones etc.
4 yr contract, fantastic research environment @crick.ac.uk
crick.wd3.myworkdayjobs.com/External/job...

'Ubiquitin Lysine-Linkages' from the review 'Ubiquitin: a structural perspective' in Molecular Cell

New to #ubiquitin? Been with it for a while? Either way this review may be for you 🤩

Excited to share our review article in @molcell.bsky.social, diving deep into everything #ubiquitin
Read here 👉: kwnsfk27.r.eu-west-1.awstrack.me/L0/https:%2F...

@cellpress.bsky.social
@wehi-research.bsky.social

BioE3 strategy to find substrates of E3 ligases applied to CRBN

✋Hello! Curious about endogenous targets of CRBN? Check new preprint from @rosabarrio1.bsky.social. You will also find how those substrates change their ubiquitination upon pomalidomide treatment #ubiquitin #TPD
👇👇👇
www.biorxiv.org/content/10.1...

Beyond happy to share with you that mine and @thejoanasilva.bsky.social latest work is out in Science Advances! Thank you so much to everyone who took part in this story, especially to @liamfaller.bsky.social and Joana for all supervision. Go check it out! ☺️

Site-saturation mutagenesis of 500 human protein domains - Nature Large-scale experimental analysis of Human Domainome 1, a library containing more than 500,000 missense mutation variants across more than 500 human protein domains, reveals that 60% of pathogenic mis...

www.nature.com/articles/s41...

The ribotoxic stress response drives acute inflammation, cell death, and epidermal thickening in UV-irradiated skin in vivo The acute skin reaction to sunburn, encompassing keratinocyte cell death, inflammation, and epidermal thickening, has traditionally been ascribed to DNA damage responses. Using a mouse model deficient...

Time for our first post here 🥳 Our latest paper is online 🙌
We show that UV activates the ribotoxic stress response, which causes inflammation, cell death and thickening in skin. Read about a role for the RSR separate from DNA damage signaling in response to sunburn: ✨☀️ www.cell.com/molecular-ce...

Our latest paper, a fantastic collaboration with the Mendell Lab, is out. Great work by Xiaoqiang Zhu and Victor Cruz. We uncover how tRNA structural features in the ribosomal P-site modulate co-translational mRNA decay by the CCR4-NOT complex. #RNAsky #RNAbiology #translation #ribosome #cryoEM 1/5