Chris Lapointe

Chris Lapointe

@lapointelab.bsky.social

RNA biochemistry | Translational control | Single-molecule approaches | Dogs | Cycling. Assistant Professor, Basic Sciences Division, Fred Hutch

478 followers443 following4 posts

Chris Lapointe reposted

Harmit Singh Malik
@harmitmalik.bsky.social

Really excited to share the final version of Rechel Geiger’s PhD thesis paper with help from friends www.science.org/doi/10.1126/... Rechel is now back in medical school training to become a kickass physician-scientist

science.orgHeterozygous and generalist MxA super-restrictors overcome breadth-specificity trade-offs in antiviral restrictionTwo evolutionary strategies allow the antiviral protein MxA to evolve simultaneous super-restriction against multiple viruses.
Chris Lapointe
@lapointelab.bsky.social

A fun collaboration with @rasilab.bsky.social led by Rachael Bakker. We used an RNA base editor to analyze at scale how substitutions within an RNA or RNA-binding protein affect binding. doi.org/10.1101/2025...

Subramaniam Lab@rasilab.bsky.social

Excited to share the work of postdoc Rachael Bakker in collaboration with @lapointelab.bsky.social! We show that RNA base editors can be repurposed for deep mutational scanning of RNA-RBP interactions at scale both in vitro and in vivo. www.biorxiv.org/content/10.1...

biorxiv.orgDeaminase-based RNA recording enables high throughput mutational profiling of protein-RNA interactionsProtein-RNA interactions govern nearly every aspect of RNA metabolism and are frequently dysregulated in disease. While individual protein residues and RNA nucleotides critical for these interactions ...

Chris Lapointe reposted

Subramaniam Lab
@rasilab.bsky.social

Excited to share the work of postdoc Rachael Bakker in collaboration with @lapointelab.bsky.social! We show that RNA base editors can be repurposed for deep mutational scanning of RNA-RBP interactions at scale both in vitro and in vivo. www.biorxiv.org/content/10.1...

biorxiv.orgDeaminase-based RNA recording enables high throughput mutational profiling of protein-RNA interactionsProtein-RNA interactions govern nearly every aspect of RNA metabolism and are frequently dysregulated in disease. While individual protein residues and RNA nucleotides critical for these interactions ...

Chris Lapointe reposted

Shicheng Guo
@shihcheng.bsky.social

Explore stabilized biomolecules! Cryo-EM shows Tetrahymena ribozyme at 2.2/2.3Å, revealing complex water networks and interactions. PMID:40068818, Nature 2025, @Nature https://doi.org/10.1038/s41586-025-08855-w #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

doi.orgComplex water networks visualized by cryogenic electron microscopy of RNA | NatureThe stability and function of biomolecules are directly influenced by their myriad interactions with water1–16. In this study, we investigated water through cryogenic electron microscopy (cryo-EM) on a highly solvated molecule, the Tetrahymena ribozyme, determined at 2.2 and 2.3 Å resolutions. By employing segmentation-guided water and ion modeling (SWIM)17,18, an approach combining resolvability and chemical parameters, we automatically modeled and cross-validated water molecules and Mg2+ ions in the ribozyme core, revealing the extensive involvement of water in mediating RNA non-canonical interactions. Unexpectedly, in regions where SWIM does not model ordered water, we observed highly similar densities in both cryo-EM maps. In many of these regions, the cryo-EM densities superimpose with complex water networks predicted by molecular dynamics (MD), supporting their assignment as water and suggesting a biophysical explanation for their elusiveness to conventional atomic coordinate mod

Chris Lapointe reposted

Edward Wallace
@ewjwallace.bsky.social

Translation meeting in Edinburgh (that I'm co-organising). Invited speakers include Allen Buskirk on his deep mechanistic work on prokarotic translation, Karen Merchante on plant ribosomal proteins and their effect, and the UK Translation community bringing their best science! #RNAbiology #ribosome

Biochemical Society@biochemsoc.bsky.social

Are you registered for the 30th Translation UK meeting? This year, our ever-popular conference is taking place at the incredible University of Edinburgh! Be quick - abstract submission and earlybird discount ends 30 April. 🧪 Register today: www.eventsforce.net/biochemsoc/2...

Chris Lapointe reposted

brangwynnelab.bsky.social
@brangwynnelab.bsky.social

What drives cytoplasmic mRNA organization? We created unbiased, genome-wide maps of mesoscale RNA-RNA spatial proximity, revealing impact of encoded protein function. Fantastic work from @lindsayabecker.bsky.social @sofiquinodoz.bsky.social @davidaknowles.bsky.social www.biorxiv.org/content/10.1...

biorxiv.orgGenome-wide mapping of mesoscale neuronal RNA organization and condensationSubcellular RNA organization can affect critical cellular functions. However, our understanding of RNA microenvironments, particularly biomolecular condensates, remains limited, largely due to a lack ...

Chris Lapointe reposted

Mark Dawson
@mafdawson.bsky.social

Why can a human tolerate a drug that globally inhibits transcription? Why do transcription inhibitors not cure cancer? Our first paper of 2025 may help explain (some) of this! So incredibly proud of @tobiaswilliams.bsky.social & Ewa Michalak who led the work! www.cell.com/molecular-ce...

cell.commRNA export factors store nascent transcripts within nuclear speckles as an adaptive response to transient global inhibition of transcriptionTranscription inhibitors also disrupt nuclear export. Here, Williams et al. reveal that mRNA export factors sense transcription inhibition and adapt by storing mature export-competent mRNA in nuclear speckles. This enables rapid release when transcription resumes and ensures retention of cellular identity and viability during a transient global transcription insult.

Chris Lapointe reposted

Fred Hutch
@fredhutch.org

In new work published today in @nature.com, researchers in @hutchbasicsci.bsky.social discover that most transcription factors in budding yeast don’t follow the textbook example of binding close to the genes they regulate. www.fredhutch.org/en/news/cent...

fredhutch.orgRewriting the story about the molecules that turn genes on and offA study by researchers at Fred Hutch Cancer Center published in Nature revises the standard story about transcription factors binding close to the genes they regulate. That is true only for a small su...

Chris Lapointe reposted

Emmanuel Margeat
@emmanuelmargeat.bsky.social

Our new study is out ! We combined #smFRET and #cryoEM to unveil the initial steps of transcription initiation in M. Tuberculosis. Fantastic work by Rishi Vishwakarma and collaboration with Konstantin Brodolin at @irim-life.bsky.social @membranesbiophy.bsky.social academic.oup.com/nar/article/...

academic.oup.comSingle-stranded DNA drives σ subunit loading onto mycobacterial RNA polymerase to unlock initiation-competent conformationsAbstract. Initiation of transcription requires the formation of the “open” promoter complex (RPo). For this, the σ subunit of bacterial RNA polymerase (RNA

Chris Lapointe reposted

Eugene Valkov
@eugenevalkov.bsky.social

This is a cool story! #RNAsky #RNAbiology

Matthew Alexander, PhD@mattmuscleguy.bsky.social

New #ScienceTM paper: Pentatricopeptide repeat protein targeting CUG repeat RNA ameliorates RNA toxicity in a myotonic dystrophy type 1 mouse model. #Myoblue tinyurl.com/4sf3rps8

tinyurl.comPentatricopeptide repeat protein targeting CUG repeat RNA ameliorates RNA toxicity in a myotonic dystrophy type 1 mouse modelAAV9-mediated systemic delivery of a protein that targets CUG repeat RNA ameliorates myotonia in a mouse model of myotonic dystrophy.

Chris Lapointe reposted

Sue Biggins
@suebiggins.bsky.social

Terrific findings from Steve Hahn's lab in @hutchbasicsci.bsky.social!

Fred Hutch@fredhutch.org

In new work published today in @nature.com, researchers in @hutchbasicsci.bsky.social discover that most transcription factors in budding yeast don’t follow the textbook example of binding close to the genes they regulate. www.fredhutch.org/en/news/cent...

fredhutch.orgRewriting the story about the molecules that turn genes on and offA study by researchers at Fred Hutch Cancer Center published in Nature revises the standard story about transcription factors binding close to the genes they regulate. That is true only for a small su...

Chris Lapointe reposted

Billy Li
@dsrna.bsky.social

I’m excited that this review co-written with my colleague and friend Carl Walkley is now published! We focused on genetic studies, from mouse to human, that uncover the functional importance and mechanisms of RNA editing enzyme ADAR1 and reveal exciting therapeutic potential. #ADAR #RNAediting

Nature Reviews Genetics@natrevgenet.nature.com

New online! Leveraging genetics to understand ADAR1-mediated RNA editing in health and disease

nature.comLeveraging genetics to understand ADAR1-mediated RNA editing in health and diseaseNature Reviews Genetics, Published online: 14 April 2025; doi:10.1038/s41576-025-00830-5ADAR1-mediating RNA editing enables the cell to distinguish between endogenous and viral RNA. Li and Walkley review findings from human and mouse genetics that have revealed the mechanisms of ADAR1-mediated RNA editing, which are now providing insights for the development of potential therapies that target these mechanisms.

Chris Lapointe reposted

Vijay Ramani
@vram142.bsky.social

To the top of the "to-read" list. Looks like a heroic amount of work from the Hahn lab (large-scale ChEC-seq compendium!) www.nature.com/articles/s41...

nature.comLow overlap of transcription factor DNA binding and regulatory targets - NatureA near-complete survey of transcription factor activities in Saccharomyces cerevisiae reveals that most transcription factors have both activator and repressor activities and limited overlap between t...

Chris Lapointe reposted

Brian Carrick
@bcarrick.bsky.social

Happy to see this work published in RNA, and thanks to the editors for the interview/Meet the First Author Feature! Surprisingly, we found that mutating an RNA binding protein's ability to bind RNA did not remove all biological function. #RNAsky #RNAbiology. rnajournal.cshlp.org/content/31/5...

rnajournal.cshlp.orgThe PUF RNA-binding protein, FBF-2, maintains stem cells without binding to RNA A monthly journal publishing high-quality, peer-reviewed research on all topics related to RNA and its metabolism in all organisms

Chris Lapointe reposted

Olivier Duss
@olivierduss.bsky.social

Ever wondered how several individual RBPs cooperate to repress translation? Lead by @marcopayr.bsky.social and in great collaboration with @hennig-lab.bsky.social, we simultaneously tracked the binding of several proteins to single mRNA molecules in real-time! www.biorxiv.org/content/10.1...

Marco Payr@marcopayr.bsky.social

In a collaboration between the @hennig-lab.bsky.social and @olivierduss.bsky.social labs we revealed how proteins work together to control gene expression through mRNA translation repression! Using single-molecule microscopy, we watched individual molecules in action. doi.org/10.1101/2025... 🧵

Chris Lapointe reposted

Michael Kearse
@michaelkearse.bsky.social

New pre-print from the lab with some great collaborators. Julia worked so hard!

bioRxiv Biochemistry@biorxiv-biochem.bsky.social

An autism spectrum disorder mutation in Topoisomerase 3B causes accumulation of covalent mRNA intermediates by disrupting metal binding within the zinc finger domain https://www.biorxiv.org/content/10.1101/2025.04.11.647616v1

Chris Lapointe reposted

Lew Lab @ WashU
@lewlab.com

A wonderful collaboration between us, @rohitpappu68.bsky.social and the Knowles lab is now online, exploring anisotropies of molecules at the interfaces of RNA condensates! Congratulations Nadia, Mina, and Yuanxin! @washuengineers.bsky.social @washu.bsky.social

Rohit V. Pappu@rohitpappu68.bsky.social

We investigated the interfacial orientations of scaffold molecules vs. adsorbents in model condensates formed by pairs of RNA molecules with PEG. Experiments identify purine-rich RNAs as scaffolds & pyrimidine-rich RNAs as adsorbents that undergo wetting transitions. www.nature.com/articles/s41...

nature.comDifferential interactions determine anisotropies at interfaces of RNA-based biomolecular condensates - Nature CommunicationsExperiments and computations show that the organization and dynamics of molecules within and at interfaces of biomolecular condensates are governed by differential interaction strengths leading to the...

Chris Lapointe reposted

Rohit V. Pappu
@rohitpappu68.bsky.social

We investigated the interfacial orientations of scaffold molecules vs. adsorbents in model condensates formed by pairs of RNA molecules with PEG. Experiments identify purine-rich RNAs as scaffolds & pyrimidine-rich RNAs as adsorbents that undergo wetting transitions. www.nature.com/articles/s41...

nature.comDifferential interactions determine anisotropies at interfaces of RNA-based biomolecular condensates - Nature CommunicationsExperiments and computations show that the organization and dynamics of molecules within and at interfaces of biomolecular condensates are governed by differential interaction strengths leading to the...

Chris Lapointe reposted

Wilson Lab
@wilsonlab.bsky.social

Fresh off the press…our latest study on the Structure of a Gcn2 dimer in complex with the large 60S ribosomal subunit | great collaboration with inada and Zaher labs. Data collected by Bertrand Beckert at the DCI EPFL www.pnas.org/doi/10.1073/...

pnas.orgStructure of a Gcn2 dimer in complex with the large 60S ribosomal subunit | PNASThe integrated stress response (ISR) is a central signaling network that enables eukaryotic cells to respond to a variety of different environmenta...

Chris Lapointe reposted

Josh Mendell
@mendell-lab.bsky.social

It's difficult to focus on science with everything going on, but I still enjoy hearing about other people's work here, so I want to continue sharing ours. Congrats to postdoc Jong-Sun Lee for his outstanding work published in @cp-molcell.bsky.social! Details in thread👇 www.cell.com/molecular-ce...

cell.comAn ultraconserved snoRNA-like element in long noncoding RNA CRNDE promotes ribosome biogenesis and cell proliferationCancer cells frequently enhance ribosome production to support rapid growth. Here, Lee et al. demonstrate that an isoform of lncRNA CRNDE containing an ultraconserved element (CRNDEUCE) promotes 60S r...

Chris Lapointe reposted

John Janetzko
@jjanetzko.bsky.social

Our lab's first paper (w @NLKProteomics) is officially online at Analytical Chem today!! @an_chem Excited for the opportunities this work brings to profiling heterogeneous membrane proteins like GPCRs. @cu-bmg.bsky.social @cupharmacology.bsky.social pubs.acs.org/doi/full/10....

pubs.acs.orgCapillary Zone Electrophoresis-Mass Spectrometry of Intact G Protein-Coupled Receptors Enables Proteoform ProfilingG protein-coupled receptors (GPCRs) are the largest class of integral membrane receptors and responsible for transmitting diverse signals in response to extracellular stimuli. Post-translational modif...
John Janetzko@jjanetzko.bsky.social

As a hard pivot from the dog/child action, here's some science to share with ya'll. Excited to share our work on developing a practical approach to resolving intact GPCR proteoforms: go.shr.lc/416MyyQ A short 🧵

go.shr.lcCapillary Zone Electrophoresis-Mass Spectrometry of Intact G Protein-Coupled Receptors Enables Proteoform ProfilingG protein-coupled receptors (GPCRs) are the largest class of integral membrane receptors and responsible for transmitting diverse signals in response to extracellular stimuli. Post-translational modif...

Chris Lapointe reposted

Iain Cheeseman
@iaincheeseman.bsky.social

Countdown to an epic new pre-print. Mitochondria are cells within our cells. They need the same core activities - replication, transcription, translation. How do cells enable these diverse activities in both compartments? We uncover an unexpected + broad strategy with ancient origins. Stay tuned!

Chris Lapointe reposted

PLOS Biology
@plosbiology.org

How does the regulation of RNA stability contribute to cortical development? This study profiles the #RNAstability landscape of the #cortex across development, revealing that the CCR4-NOT deadenylase complex is essential for corticogenesis in vivo 🧪 @plosbiology.org plos.io/3EtZjvN

Chris Lapointe
@lapointelab.bsky.social

Congrats, Sam! Exciting news!

Samara Reck-Peterson@samreckpeterson.bsky.social

I am excited for this opportunity to chair the Department of Biochemistry and Biophysics at Weill Cornell Medicine! news.weill.cornell.edu/news/2025/01...

news.weill.cornell.eduDr. Samara Reck-Peterson Named Chair of the Department of Biochemistry and Biophysics at Weill Cornell MedicineThe newly configured department marshals biochemists, biophysicists and experts in protein engineering and imaging to drive discoveries in the basic mechanisms of cell function.
Chris Lapointe
@lapointelab.bsky.social

Congrats @marvintanenbaum.bsky.social and team! Impressive work, with important implications on different kinds of ribosome collisions.

Marvin Tanenbaum@marvintanenbaum.bsky.social

Our paper on Stopless-ORF Circular RNAs (socRNAs) is now out in Cell. By high-res tracking and comparing translation by either single or multiple ribosomes, we find that ribosomes cooperate to overcome pausing to ensure fast and efficient translation www.cell.com/cell/fulltex...

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

Chris Lapointe reposted

Lovorka Stojić
@loverna.bsky.social

📢1/12 Happy to share our first bluetutorial & our latest preprint. In this work, we discovered RSRC2 as a novel RNA-binding protein (RBP) with a dual function in cell division whose activity can be (lnc)RNA-mediated. #lncRNA #RBP #Mitosis www.biorxiv.org/content/10.1...

biorxiv.orgThe RNA-binding protein RSRC2 promotes mitotic fidelity by interacting with the lncRNA C1QTNF1-AS1Mitotic fidelity depends on proper chromosome alignment at the spindle equator, a process known as chromosome congression, driven by well-established protein networks. Whereas RNA-binding proteins and...

Chris Lapointe reposted

Bloom lab
@jbloomlab.bsky.social

In a new study led by Caelan Radford, we use deep mutational scanning to systematically compare the escape mutations from two broadly neutralizing antibodies in a clade A versus clade B HIV Envelope. www.biorxiv.org/content/10.1...

biorxiv.orgComprehensive maps of escape mutations from antibodies 10-1074 and 3BNC117 for Envs from two divergent HIV strainsAntibodies capable of neutralizing many strains of HIV are being explored as prophylactic and therapeutic agents, but viral escape mutations pose a major challenge. Efforts have been made to experimen...

Chris Lapointe reposted

Karina Jouravleva
@karinajouravleva.bsky.social

Our review on small endogenous RNAs in animals is online: www.nature.com/articles/s41.... We thank @martinjsimard.bsky.social, @svobodalab.bsky.social and the third, anonymous, reviewer for helping us improve our manuscript. @lbmcinlyon.bsky.social @cnrsbiologie.bsky.social

nature.comA guide to the biogenesis and functions of endogenous small non-coding RNAs in animals - Nature Reviews Molecular Cell BiologyMany new small RNA species and their derived fragments have been recently identified in animals. This Review discusses the biogenesis and functions of both structural small RNAs, such as tRNAs and sma...

Chris Lapointe reposted

Eva Kowalinski
@kowaeva.bsky.social

Architecture and RNA binding properties of the trypanosome nuclear cap-binding complex - key complex in the parasite’s RNA metabolism. Final peer-reviewed version is public! #RNAsky #trypsky www.nature.com/articles/s41...

nature.comStructural basis of Spliced Leader RNA recognition by the Trypanosoma brucei cap-binding complex - Nature CommunicationsBernhard et al. reveal the architecture of the tetrameric Trypanosoma brucei nuclear cap-binding complex. Using cryo-electron microscopy and biochemical assays, the researchers characterize its bindin...

Chris Lapointe reposted

Cristian Prieto-Garcia
@prieto-garcia.bsky.social

It is finally out! My first Science paper is online and it does not seem real😃. I am Incredibly happy! Really thanks to all my coauthors and special mention to my incredible supervisor Ivan Dikic for all the support and trust ! 🫶. #RNA #Proteostasis #ubiquitin #autophagy #RP doi.org/10.1126/scie...

doi.orgPathogenic proteotoxicity of cryptic splicing is alleviated by ubiquitination and ER-phagyRNA splicing enables the functional adaptation of cells to changing contexts. Impaired splicing has been associated with diseases, including retinitis pigmentosa, but the underlying molecular mechanis...

Chris Lapointe reposted

Frances Yap
@ribo1214.bsky.social

Fragmented rRNAs of apicomplexan mitoribosome. doi.org/10.1038/s414... and doi.org/10.1038/s414... 🧪 #RNASky #Ribosome

doi.orgNumerous rRNA molecules form the apicomplexan mitoribosome via repurposed protein and RNA elements - Nature CommunicationsStructure of the Toxoplasma mitoribosome made of >50 short rRNA molecules reveals evolutionary solutions to rRNA fragmentation: addition of poly A tails to rRNAs, reused rRNA sequences, and repurpo...

Chris Lapointe reposted

Frances Yap
@ribo1214.bsky.social

Rescue of stalled (damaged/intact) ribosomes by the peptide release factor PrfH (part of the PrfH-RtcB rescue-repair system). 🧪 #Ribosome doi.org/10.1101/2025...

doi.orgMolecular and structural basis of a subfamily of PrfH rescuing both the damaged and intact ribosomes stalled in translationIn bacteria, spontaneous mRNAs degradation and ribotoxin-induced RNA damage are two main biological events that lead to the stall of protein translation. The ubiquitous trans-translation system as wel...

Chris Lapointe reposted

Michael VanInsberghe
@mvanins.bsky.social

Several new technologies have enabled translation profiling in single cells. In our article in @natrevmcb.bsky.social, Alexander and I discuss these single-cell methods for measuring ribosome profiles, ribosome-associated transcripts, and spatial translation 🧵 www.nature.com/articles/s41...

nature.comSequencing technologies to measure translation in single cells - Nature Reviews Molecular Cell BiologyRecent sequencing-based methods, including novel ribosome profiling, ribosome affinity purification and spatial translation methods, have enabled the measurement of translation at single-cell resoluti...

Chris Lapointe reposted

Anthony Schuller
@aschuller17.bsky.social

Excited to share the 1st preprint from our incredible team at Interdict Bio as we progress novel, small-molecule sequence-selective inhibitors of translation toward the clinic to address difficult to treat cancers! #ribosome #interdictor Check out the preprint here: www.biorxiv.org/content/10.1...

biorxiv.orgContext-dependent translation inhibition as a novel oncology therapeutic modalityInhibitors of protein synthesis, including anisomycin, homoharringtonine, and other natural products bind in the peptidyl-transferase center (PTC) of the eukaryotic ribosome to inhibit translation. Re...

Chris Lapointe reposted

Anne Simon 🧪🌱🐴🦠🍊🇨🇦🇺🇦
@annealiz1.bsky.social

🧪Hey #PlantVirologists! Lets make this a great community by posting/commenting on important papers in our field (can be yours!). I'll start. PLoS Biology paper of ours describing first plant viruses using host (and not encoded) movement proteins! journals.plos.org/plosbiology/...

journals.plos.orgUmbravirus-like RNA viruses are capable of independent systemic plant infection in the absence of encoded movement proteinsThe spread of viral genomes into adjacent cells and the plant vascular system is enabled by viral movement proteins. This study shows that umbravirus-like RNA viruses can spread systemically without e...

Chris Lapointe reposted

Navtej Toor
@navtejtoor.bsky.social

Congratulations to Dan Haack and Boris Rudolfs on the new paper from our lab about the development of a scaffold enabling high resolution cryo-EM structure determination of protein-free RNAs. www.nature.com/articles/s41...

nature.comScaffold-enabled high-resolution cryo-EM structure determination of RNA - Nature CommunicationsDetermining structures of small, protein-free RNAs by cryo-EM has been challenging. Here, the authors use a group II intron scaffold to achieve high-resolution RNA structures, visualize ligand-induced...