Chris Lapointe

Heterozygous and generalist MxA super-restrictors overcome breadth-specificity trade-offs in antiviral restriction Two evolutionary strategies allow the antiviral protein MxA to evolve simultaneous super-restriction against multiple viruses.

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

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...

Deaminase-based RNA recording enables high throughput mutational profiling of protein-RNA interactions Protein-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 ...

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...

Deciphering disordered regions controlling mRNA decay in high-throughput - Nature Using high-throughput functional profiling, how disordered regions control mRNA stability and translation is explored.

Will be taking a deep dive into this today. Congrats to Joe Lobel and Nick Ingolia! #RNAsky #RNAbiology

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

Excited to share Benson’s and Maria’s work in collab w/Kostas Tzelepis: we found the nucleolar protein NPM1 is a marker of AML and can be targeted therapeutically

connecting ‘cell surface RNA biology’ to cancer biology

@natbiotech.nature.com
www.nature.com/articles/s41...

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 🧪

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

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

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...

A nuclear RNA degradation code is recognized by PAXT for eukaryotic transcriptome surveillance Soles et al. demonstrate that the combination of a 5′ splice site and a poly(A) junction constitutes a nuclear RNA degradation code that targets RNAs for degradation by the PAXT adaptor and the RNA ex...

www.cell.com/molecular-ce...

A conserved opal termination codon optimizes a temperature-dependent trade-off between protein production and processing in alphaviruses Alphaviruses optimize viral polymerase production and polyprotein processing at distinct temperatures via a premature stop codon.

Our study exploring the evolutionary mechanism of alphavirus opal codon retention is now online! www.science.org/doi/10.1126/...

mRNA export factors store nascent transcripts within nuclear speckles as an adaptive response to transient global inhibition of transcription Transcription 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.

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...

Re-adenylation by TENT5A enhances efficacy of SARS-CoV-2 mRNA vaccines - Nature Upon intramuscular administration, COVID-19 mRNA vaccines are primarily taken up by macrophages, in which the cellular machinery extends their poly(A) tails, thereby increasing mRNA stability and tran...

#RNA #RNASky

Rewriting the story about the molecules that turn genes on and off A 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...

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...

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

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/...

Interested in doing a postdoc in Seattle? Join us on May 6 for Seattle DROP, a virtual biomedical postdoc recruitment event. The first 250 US registrants enjoy lunch via delivery voucher! 🥪

All postdoc candidates are invited to attend.
👇👇👇
Registration: tinyurl.com/seattledrop25

This is a cool story! #RNAsky #RNAbiology

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

From music to molecules: Fred Hutch’s Dr. Melody Campbell’s lab is one of the only electron microscopy labs studying integrins Growing up, Dr. Melody Campbell, 38, was part of the Campbell Quartet.

Inspirational spotlight on @hutchbasicsci.bsky.social faculty member Melody Campbell!
nwasianweekly.com/2025/03/from...

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

Small-molecule RNA therapeutics to target prostate cancer Kuzuoglu-Ozturk et al. showcase a therapeutic approach, “translatome therapy,” to combat lethal prostate cancer. Zotatifin, a clinical molecule, targets the RNA-helicase eIF4A. Zotatifin decreases the...

www.cell.com/cancer-cell/...

Interested in postdoc opportunities in Seattle, WA? Join us May 6th for Seattle DROP, a virtual event about biomedical research in Seattle. Hear from recruiting faculty, finding the right mentor and enjoy lunch on us via a delivery voucher within the US!

Registration: tinyurl.com/seattledrop25

Low overlap of transcription factor DNA binding and regulatory targets - Nature A 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...

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...

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...

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...

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

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

Differential interactions determine anisotropies at interfaces of RNA-based biomolecular condensates - Nature Communications Experiments 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...

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...

Check out our preprint at BioRxiv revealing mechanisms of mRNP assembly during translation repression: (www.biorxiv.org/content/10.1...). Great collaboration with Olivier Duss (@olivierduss.bsky.social). Great Work Marco Payr (@marcopayr.bsky.social) and thanks for the video, explaining our paper.

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

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/...

An ultraconserved snoRNA-like element in long noncoding RNA CRNDE promotes ribosome biogenesis and cell proliferation Cancer 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...

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...