Chris Lapointe
@lapointelab.bsky.social
RNA biochemistry | Translational control | Single-molecule approaches | Dogs | Cycling. Assistant Professor, Basic Sciences Division, Fred Hutch
Reposted by Chris Lapointe
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
www.science.org/doi/10.1126/...
Rechel is now back in medical school training to become a kickass physician-scientist
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.
www.science.org
May 5, 2025 at 9:48 PM
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
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...
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...
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...
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...
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 ...
www.biorxiv.org
May 2, 2025 at 1:05 AM
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...
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...
Reposted by Chris Lapointe
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...
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...
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 ...
www.biorxiv.org
May 2, 2025 at 12:16 AM
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...
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...
Reposted by Chris Lapointe
Will be taking a deep dive into this today. Congrats to Joe Lobel and Nick Ingolia! #RNAsky #RNAbiology
www.nature.com/articles/s41...
www.nature.com/articles/s41...
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.
www.nature.com
April 24, 2025 at 10:53 AM
Will be taking a deep dive into this today. Congrats to Joe Lobel and Nick Ingolia! #RNAsky #RNAbiology
www.nature.com/articles/s41...
www.nature.com/articles/s41...
Reposted by Chris Lapointe
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...
connecting ‘cell surface RNA biology’ to cancer biology
@natbiotech.nature.com
www.nature.com/articles/s41...
April 23, 2025 at 11:44 AM
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...
connecting ‘cell surface RNA biology’ to cancer biology
@natbiotech.nature.com
www.nature.com/articles/s41...
Reposted by Chris Lapointe
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 🧪
Complex water networks visualized by cryogenic electron microscopy of RNA | Nature
The 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
doi.org
April 3, 2025 at 2:10 PM
Reposted by Chris Lapointe
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
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
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...
Register today: www.eventsforce.net/biochemsoc/2...
April 22, 2025 at 4:38 PM
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
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
Reposted by Chris Lapointe
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...
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 ...
www.biorxiv.org
April 21, 2025 at 1:48 PM
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...
Reposted by Chris Lapointe
Reposted by Chris Lapointe
Our study exploring the evolutionary mechanism of alphavirus opal codon retention is now online! www.science.org/doi/10.1126/...
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.
www.science.org
April 18, 2025 at 10:43 PM
Our study exploring the evolutionary mechanism of alphavirus opal codon retention is now online! www.science.org/doi/10.1126/...
Reposted by Chris Lapointe
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...
So incredibly proud of @tobiaswilliams.bsky.social & Ewa Michalak who led the work!
www.cell.com/molecular-ce...
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.
www.cell.com
January 2, 2025 at 8:03 PM
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...
So incredibly proud of @tobiaswilliams.bsky.social & Ewa Michalak who led the work!
www.cell.com/molecular-ce...
Reposted by Chris Lapointe
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...
@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...
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...
www.fredhutch.org
April 16, 2025 at 4:43 PM
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...
@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...
Reposted by Chris Lapointe
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/...
@irim-life.bsky.social
@membranesbiophy.bsky.social
academic.oup.com/nar/article/...
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
academic.oup.com
April 17, 2025 at 4:38 PM
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/...
@irim-life.bsky.social
@membranesbiophy.bsky.social
academic.oup.com/nar/article/...
Reposted by Chris Lapointe
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
All postdoc candidates are invited to attend.
👇👇👇
Registration: tinyurl.com/seattledrop25
Seattle DROP: Discover Research Opportunities for Postdocs
tinyurl.com
April 17, 2025 at 4:34 PM
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
All postdoc candidates are invited to attend.
👇👇👇
Registration: tinyurl.com/seattledrop25
Reposted by Chris Lapointe
This is a cool story! #RNAsky #RNAbiology
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
Pentatricopeptide repeat protein targeting CUG repeat RNA ameliorates RNA toxicity in a myotonic dystrophy type 1 mouse model
AAV9-mediated systemic delivery of a protein that targets CUG repeat RNA ameliorates myotonia in a mouse model of myotonic dystrophy.
tinyurl.com
April 16, 2025 at 8:33 PM
This is a cool story! #RNAsky #RNAbiology
Reposted by Chris Lapointe
Terrific findings from Steve Hahn's lab in @hutchbasicsci.bsky.social!
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...
@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...
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...
www.fredhutch.org
April 16, 2025 at 4:50 PM
Terrific findings from Steve Hahn's lab in @hutchbasicsci.bsky.social!
Reposted by Chris Lapointe
Inspirational spotlight on @hutchbasicsci.bsky.social faculty member Melody Campbell!
nwasianweekly.com/2025/03/from...
nwasianweekly.com/2025/03/from...
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.
nwasianweekly.com
March 10, 2025 at 5:32 PM
Inspirational spotlight on @hutchbasicsci.bsky.social faculty member Melody Campbell!
nwasianweekly.com/2025/03/from...
nwasianweekly.com/2025/03/from...
Reposted by Chris Lapointe
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
New online! Leveraging genetics to understand ADAR1-mediated RNA editing in health and disease
Leveraging genetics to understand ADAR1-mediated RNA editing in health and disease
Nature 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.
www.nature.com
April 15, 2025 at 1:45 AM
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
Reposted by Chris Lapointe
Reposted by Chris Lapointe
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
Registration: tinyurl.com/seattledrop25
Seattle DROP: Discover Research Opportunities for Postdocs
tinyurl.com
April 16, 2025 at 3:28 PM
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
Registration: tinyurl.com/seattledrop25
Reposted by Chris Lapointe
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...
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...
www.nature.com
April 16, 2025 at 4:04 PM
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...
Reposted by Chris Lapointe
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.org/content/31/5...
The 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
rnajournal.cshlp.org
April 16, 2025 at 3:19 PM
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.org/content/31/5...
Reposted by Chris Lapointe
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...
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...
April 12, 2025 at 11:29 AM
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...
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...
Reposted by Chris Lapointe
New pre-print from the lab with some great collaborators. Julia worked so hard!
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
April 12, 2025 at 3:28 PM
New pre-print from the lab with some great collaborators. Julia worked so hard!