Stirling Churchman
@fiddle
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@HMSgenetics professor. Interested in RNA dynamics across the cell esp. nuclear transcription and splicing and mitochondrial gene expression. (she/her)
Cambridge, MA
Joined November 2007
I'm thrilled to see the cover of @NatureSMB this month! My sibling Leidy Churchman made this special painting to illustrate our latest work on the packaging of mitochondrial DNA. Both works are nicely described in the "Musings on art and science" editorial https://t.co/qovSVFRxyq
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An exciting study driven by the close collaboration of first authors Erin Duffy ( https://t.co/fJ0jmIQS0p) and Inés Patop (@inespatop)! And thanks to our other colleagues for making this such a comprehensive study. (11/11)
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This work reveals RNA stability as a "hidden layer" of gene regulation that: 1) Operates independently of transcription 2) Works locally in neuronal processes 3) Is disrupted in neurodevelopmental disorders 4) Expands our view of activity-dependent plasticity (10/11)
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Importantly, HuD-bound mRNAs are enriched for autism spectrum disorder (ASD) risk genes, and ASD variants can alter RNA stability regulation, implicating this pathway in neurodevelopmental disorders. (9/11)
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How does activity change HuD function? Not by changing HuD levels, but by reorganizing its protein partners. Microscopy and IP-MS support a model where activity recruits HuD into RNA granules, stabilizing HuD-bound mRNAs by protecting them from degradation. (8/11)
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We found that activity-dependent gene expression is modulated in both soma and distal processes (dendrites and axons), suggesting neurons may coordinate RNA stability, transport, and translation to adjust protein levels locally. (7/11)
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To gain some mechanistic insight, we used MPRAs, machine learning, RIP-seq and metabolic labeling and identified the RNA binding protein HuD as a key regulator of activity-dependent RNA stability. (6/11)
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And we did some in vivo validation: We also see effects on RNA stability in vivo in response to novel environment exploration, meaning this isn’t just a phenomenon in primary neurons, it also occurs in a physiologically relevant learning paradigm in the intact brain. (5/11)
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RNA stability changes weren’t just a side effect. For ~10% of activity-dependent transcripts, stability mattered more than transcription for determining RNA levels, challenging the transcription-centric view of gene regulation in this process. (4/11)
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Of ~5,000 activity-regulated transcripts, two thirds showed changes in transcription, which was expected. Unexpectedly, ~1,000 genes were regulated by RNA stability.(3/11)
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When neurons fire, they need to rapidly change which genes are expressed to support processes like long-term memory. Transcriptional responses are well studied, but what about other steps in the RNA life cycle? (2/11)
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Our new pre-print from the Greenberg and Churchman labs shows that activity-dependent modulation of RNA stability is a major, and underappreciated, mechanism of gene regulation in neurons. Tutorial below 👇 https://t.co/DEvnKvqjJz (1/11)
biorxiv.org
Neuronal activity shapes brain development and refines synaptic connectivity in part through dynamic changes in gene expression. While activity-regulated transcriptional programs have been extensiv...
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In this study, the spatial distribution of mitochondrial-encoded RNAs is investigated and shows that upon transcription arrest, RNAs form granules that show protectivity for transcripts. @Harvardmed @fiddle
https://t.co/LN4k20EDAM
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Mitochondrial RNAs can be found in mitochondrial RNA granules (MRGs) where they are processed. However, here the authors show that during transcription arrest, mt-mRNAs form granules distinct from MRGs. @Harvardmed @fiddle
https://t.co/7Qant1ylY3
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Happy to share our new review!
To launch the collection, our review "The regulation and function of post-transcriptional RNA splicing" by Karine Choquet, @inespatop & Stirling Churchman @fiddle ( https://t.co/flccIt1ZnI) will be free for 1 month
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I wrote this @WSJopinion piece with my father-in-law, Jack Strominger. "Science Suffers With Trump's Funding Freeze". America’s scientific enterprise demands reliable stewardship, not destabilizing political intervention. Please RT!
wsj.com
America’s scientific enterprise demands reliable stewardship, not destabilizing political intervention.
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RNA polymerases reshape chromatin architecture and couple transcription on individual fibers https://t.co/0ZLfgkKhHZ
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Online Now: RNA polymerases reshape chromatin architecture and couple transcription on individual fibers https://t.co/zpVZwFK40Q
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Congratulations, and many thanks to all who participated including @mtcicero26 @rsisaac. Another wonderful and fruitful collaboration with @stergachislab!
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I’m thrilled to share our latest paper analyzing RNA polymerase globally at single-molecule resolution that provides a glimpse into the vast potential of single-molecule genomics. See tweets below for the overview, and read the paper for the full story!
How does Pol II navigate the crowded, complex chromatin environment, surrounded by nucleosomes and other transcriptional activity? We are excited to share our preprint, a fantastic collaboration with @stergachislab, led by Tommy Tullius @mtcicero26
https://t.co/Z4CSiU9IMP (1/5)
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