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David Bartel's Lab

@bartellab.bsky.social
674 followers 164 following 32 posts

David Bartel's lab @WhiteheadInst @MIT @HHMI | microRNAs, mRNAs, and other RNAs

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David Bartel's Lab @bartellab.bsky.social · 16/06/2026
In the second, we built a platform to rapidly replace endogenous PABPC1 & PABPC4 with designed variants in human cells. We leverage PABPC paralogs, domain deletions, PTM-disrupting mutants, and titrated variant expression to understand RRM4 in the cellular context. www.biorxiv.org/content/10.6...
biorxiv.org
Dissection of Poly(A)-binding protein (PABPC) cellular function using degron-mediated depletion with replacement
Cytoplasmic poly(A)-binding proteins (PABPCs) are essential and highly abundant regulators of mRNA stability and translation, but their cellular functions have been difficult to dissect due to slow tu...
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David Bartel's Lab @bartellab.bsky.social · 16/06/2026
In the first, we measured deadenylation rates across ~39K human 3′ UTR sequences and found that the poly(A)-proximal sequence tunes PABPC1 binding propensity, which in turn modulates deadenylation rate. A PABP-1212 mutant lacking UTR binding abolishes this effect. www.biorxiv.org/content/10.6...
biorxiv.org
The molecular determinants of PABPC-mediated deadenylation rate
Deadenylation, the enzymatic shortening of the poly(A) tail, is typically the first committed step of mRNA decay. Deadenylation rates span nearly a 1000-fold range between transcripts and are governed...
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David Bartel's Lab @bartellab.bsky.social · 16/06/2026
Two new preprints featuring work from @ryanymuller.bsky.social on PABPC biology! With important contributions from @eugenevalkov.bsky.social, Tanner Myers, and @kxwang.bsky.social
biorxiv.org
The molecular determinants of PABPC-mediated deadenylation rate
Deadenylation, the enzymatic shortening of the poly(A) tail, is typically the first committed step of mRNA decay. Deadenylation rates span nearly a 1000-fold range between transcripts and are governed...
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David Bartel's Lab @bartellab.bsky.social · 30/03/2026
Our work investigating mRNA 3' UTRs that trigger target-directed miRNA degradation is now published! genesdev.cshlp.org/content/earl...
genesdev.cshlp.org
mRNA 3′ UTRs direct microRNA degradation to participate in imprinted gene networks and regulate growth
A biweekly scientific journal publishing high-quality research in molecular biology and genetics, cancer biology, biochemistry, and related fields
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David Bartel's Lab @bartellab.bsky.social · 19/03/2026
Our work on the E3 ligase mechanism of target-directed microRNA degradation is now published! Amazing collaboration with Brenda Schulman’s lab led by @jakobfarnung.bsky.social and @elenaslo.bsky.social, with special thanks to @wyppeter.bsky.social, Lianne Blodgett, and Daniel Lin! tinyurl.com/Z8TDMD
tinyurl.com
The E3 ubiquitin ligase mechanism specifying targeted microRNA degradation - Nature
Target-directed microRNA degradation is driven by the atypical ZSWIM8–CUL3 E3 ubiquitin ligase that uses a two-RNA-factor authentication mechanism to specifically recognize AGO–miRNA–trigger...
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Reposted by David Bartel's Lab
Xuebing Wu @xuebingwu.bsky.social · 31/01/2026
Does the noncoding genome actually carry more genetic information than coding seqs? Motivated by this question we mutated every bp in the 10kb MYC locus. Results are even more exciting: Decoding the MYC locus reveals a druggable ultraconserved RNA element www.biorxiv.org/content/10.6...
biorxiv.org
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David Bartel's Lab @bartellab.bsky.social · 23/01/2026
Huge thanks to @maxewilkinson.bsky.social for making this work possible! (4/4)
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David Bartel's Lab @bartellab.bsky.social · 23/01/2026
In the process of solving this mystery, we discovered a new, atypical conformation of the spliceosome and discovered that the spliceosome has a surprising propensity to reassemble on excised linear introns in both stressed and unstressed conditions. (3/4)
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David Bartel's Lab @bartellab.bsky.social · 23/01/2026
In budding yeast cultured under saturation or other prolonged stresses, ~10% of introns accumulate post-splicing as stable, linear RNAs that are protected by the spliceosome. We set out to understand how these stable introns remain associated with the spliceosome and escape canonical RNA decay.(2/4)
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David Bartel's Lab @bartellab.bsky.social · 23/01/2026
We’re excited to share our latest preprint on the mechanism of excised linear intron stabilization in yeast! This work was led by PhD student @glennli.bsky.social and was a wonderful collaboration with @maxewilkinson.bsky.social. Link: www.biorxiv.org/content/10.6... (1/4)
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Reposted by David Bartel's Lab
Iain Cheeseman @iaincheeseman.bsky.social · 23/01/2026
First preprint of the year! New work from @jimmy-ly.bsky.social revealing unexpected roles for 5' UTR length in controlling alternate translational isoforms - important implications for both physiological cell function and rare disease. Small changes -> big impacts. www.biorxiv.org/content/10.6...
biorxiv.org
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Reposted by David Bartel's Lab
Eugene Valkov @eugenevalkov.bsky.social · 18/01/2026
We are looking for a postdoc to work on mechanisms of #RNA decay in cancer using #cryoEM with #nanobodies and #minibinders! Please RT
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David Bartel's Lab @bartellab.bsky.social · 14/01/2026
We find that disrupting the miR-200–ZEB1 double-negative feedback loop leads to anovulatory infertility and widespread gene expression changes in the mouse pituitary. This study demonstrates the dramatic phenotypic and molecular consequences of disrupting repression of a single miRNA target. (2/2)
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David Bartel's Lab @bartellab.bsky.social · 14/01/2026
Check our latest collaboration with the Kleaveland Lab (kleavelandlab.org), led by Joanna Stefano and Lara Elcavage: academic.oup.com/nar/article/... (1/2)
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David Bartel's Lab @bartellab.bsky.social · 06/01/2026
Huge thanks to Brenda Schulman and @jakobfarnung.bsky.social for the exceptionally collaborative effort from start to finish. We also thank @wyppeter.bsky.social, Lianne Blodgett, and Daniel Lin for their invaluable contributions to this work! (5/5)
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David Bartel's Lab @bartellab.bsky.social · 06/01/2026
Our results establish AGO binding and polyubiquitylation as the key regulatory steps of TDMD, define a unique class of cullin–RING E3 ligases that depend on CUL3 and ELOB/C, and reveal generalizable RNA- and protein-mediated interactions that specify AGO degradation with exquisite selectivity. (4/5)
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David Bartel's Lab @bartellab.bsky.social · 06/01/2026
We demonstrate selective binding of ZSWIM8 to a human AGO–microRNA–trigger complex for CUL3-mediated polyubiquitylation of the AGO protein. Furthermore, cryo-EM analyses reveal how ZSWIM8 recognizes the distinct AGO and RNA conformations shaped by pairing of the microRNA to the trigger. (3/5)
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David Bartel's Lab @bartellab.bsky.social · 06/01/2026
The ZSWIM8 E3 ligase was known to cause degradation of AGO–microRNA complexes bound to trigger RNAs. However, whether and how ZSWIM8 directly recognizes these complexes among the preponderance of non-trigger-bound AGO–microRNA complexes in the cell has been a mystery. (2/5)
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David Bartel's Lab @bartellab.bsky.social · 06/01/2026
We are thrilled to share our latest work uncovering the mechanistic basis of target-directed microRNA degradation (TDMD). This work was driven by @jakobfarnung.bsky.social and @elenaslo.bsky.social in a fantastic collaboration with Brenda Schulman's lab. tinyurl.com/E3TDMD (1/5)
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Iain Cheeseman @iaincheeseman.bsky.social · 07/11/2025
From an accidental discovery of hidden biology to a new framework to understanding and diagnosing rare disease. Thrilled to share the most recent work from our lab and the amazing Jimmy Ly. wi.mit.edu/news/alterna...
wi.mit.edu
Alternate proteins from the same gene contribute differently to health and rare disease | Whitehead Institute
Iain Cheeseman and colleagues reveal the underappreciated role of single genes producing multiple proteins in atypical presentations of rare disease, and present case studies of affected patients thro...
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David Bartel's Lab @bartellab.bsky.social · 07/11/2025
Check out related work by the Mendell lab (@mendell-lab.bsky.social) and the Xie lab: www.biorxiv.org/content/10.1..., www.biorxiv.org/content/10.1... (3/3)
biorxiv.org
Plagl1 and Lrrc58 control mammalian body size by triggering target-directed microRNA degradation of miR-322 and miR-503
Precise control of microRNA (miRNA) expression is critical during development. An important mechanism of miRNA regulation is target-directed microRNA degradation (TDMD), a pathway in which the binding...
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David Bartel's Lab @bartellab.bsky.social · 07/11/2025
We identify 5 sites in 3' UTRs of mRNAs that trigger target-directed microRNA degradation (TDMD) of miR-335-3p, miR-322, and miR-503, uncovering noncoding functions of these mRNAs. This study positions TDMD within imprinted gene networks on the battleground of parental conflict (2/3)
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David Bartel's Lab @bartellab.bsky.social · 07/11/2025
Check out the latest work from our lab, led by Daniel Lin and Lara Elcavage: www.biorxiv.org/content/10.1... (1/3)
biorxiv.org
mRNA 3′ UTRs direct microRNA degradation to participate in imprinted gene networks and regulate growth
MicroRNAs direct downregulation of target mRNAs. Sometimes, however, this regulatory paradigm inverts, and a target RNA triggers the degradation of a microRNA. This target-directed microRNA degradatio...
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David Bartel's Lab @bartellab.bsky.social · 13/10/2025
We've uncovered two mechanisms that coronaviruses use to solve the “tailomere problem” and identified an mRNA degradation pathway that operates independently of viral protein nsp1. Many thanks to Eugene Valkov's lab (@eugenevalkov.bsky.social) for their help with this study.
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David Bartel's Lab @bartellab.bsky.social · 13/10/2025
Check out the latest work from our lab, led by Arash Latifkar @ara-latifkar.bsky.social , www.biorxiv.org/content/10.1...
biorxiv.org
mRNA poly(A)-tail length is a battleground for coronavirus–host competition
Most eukaryotic mRNAs contain a poly(A) tail, which in post-embryonic cells enhances their stability. Many cytoplasmic RNA viruses also harbor poly(A) tails on their genomic RNA and mRNAs. Here, we re...
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David Bartel's Lab @bartellab.bsky.social · 11/09/2025
Since their discovery, we have known lysosomes possess RNase activity; however, their endogenous substrates were not known. Surprisingly we found preferential targeting of specific RNAs for lysosomal degradation by autophagy and identified sequence motifs that mediate their lysosomal targeting (2/2)
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David Bartel's Lab @bartellab.bsky.social · 11/09/2025
Check out the latest work from Jordan Ray (@jordanray.bsky.social), a collaboration between our lab and David Sabatini’s lab. www.biorxiv.org/content/10.1... (1/2)
biorxiv.org
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...
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Reposted by David Bartel's Lab
Eugene Valkov @eugenevalkov.bsky.social · 13/08/2025
Delighted to present our second paper of the year. This one explores the molecular mechanism of TTP, a key post-transcriptional regulator of AU-rich mRNAs. Work led and coordinated by @filippekovic.bsky.social, in collaboration with Perry Blackshear. www.nature.com/articles/s41...
nature.com
Multivalent interactions with CCR4–NOT and PABPC1 determine mRNA repression efficiency by tristetraprolin - Nature Communications
Deadenylation leads to mRNA decay, with PABPC1 protecting the poly(A) tail, while tristetraprolin and CCR4–NOT promote deadenylation. Here, the authors describe how these three proteins interact to re...
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David Bartel's Lab @bartellab.bsky.social · 02/08/2025
We developed a neural network machine-learning model that predicts poly(A) tail-length changes in frog, mouse, and human oocytes, revealing new regulatory motifs and showing that variants disrupting tail lengthening are under negative selection, thus linking tail-length control to human fertility.
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David Bartel's Lab @bartellab.bsky.social · 02/08/2025
Check out the latest study from our lab, led by Coffee Xiang (@coffeebond007.bsky.social) www.nature.com/articles/s41... (1/2)
nature.com
PAL-AI reveals genetic determinants that control poly(A)-tail length during oocyte maturation, with relevance to human fertility - Nature Communications
Gene regulation in oocytes relies heavily on poly(A) tail-length changes. Here, the authors develop PAL-AI, a neural network model that predicts tail-length changes, identifies regulatory motifs, and ...
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Reposted by David Bartel's Lab
Iain Cheeseman @iaincheeseman.bsky.social · 23/07/2025
New preprint! We solve a mystery you didn't know existed. Mitotic cells lack new transcription but require ongoing translation. Interphase mRNA half life is only 2-4 hrs. So how do cells arrest in mitosis for hours without depleting their transcriptomes? www.biorxiv.org/content/10.1...
biorxiv.org
Global inhibition of deadenylation stabilizes the transcriptome in mitotic cells
In the presence of cell division errors, mammalian cells can pause in mitosis for tens of hours with little to no transcription, while still requiring continued translation for viability. These unique...
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David Bartel's Lab @bartellab.bsky.social · 05/04/2025
Don’t miss this Q&A with Dr. Michelle Frank (@michelle-frank.bsky.social), an awesome postdoc in our lab!
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David Bartel's Lab @bartellab.bsky.social · 15/03/2025
We report that some miRNAs are capable of high affinity binding to 3′-only sites (stretches of extensive perfect pairing to the 3′ region, without any pairing to the miRNA seed) and that these sites are functional, imparting post-transcriptional repression to site-containing reporter mRNAs. (2/2)
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David Bartel's Lab @bartellab.bsky.social · 15/03/2025
Check out the latest study from our lab, led by @mhall98.bsky.social : www.biorxiv.org/content/10.1... (1/2)
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Reposted by David Bartel's Lab
Peter Wang @wyppeter.bsky.social · 01/01/2025
Happy 2025! Excited to finally share our published slicing structure of human AGO2, the catalytic structure for RNAi by siRNAs and miRNAs. This was an amazing collab effort between @voslab.org and @bartellab.bsky.social with @amohamed98.bsky.social
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David Bartel's Lab @bartellab.bsky.social · 03/01/2025
Check out our latest paper in collaboration with @voslab.org on the cryo-EM structure of slicing by human AGO2: tinyurl.com/AGO2-slicing
tinyurl.com
The structural basis for RNA slicing by human Argonaute2
Mohamed et al. report the cryoelectron microscopy structure of human AGO2 with fully paired guide RNA. Their analysis reveals the structural basis for the slicing activity that drives RNAi, showing that the slicing-competent conformation is achieved by domain movements and RNA-protein contacts distinct from those of conformational intermediates and prokaryotic homologs.
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David Bartel's Lab @bartellab.bsky.social · 18/12/2024
Thank you, Eugene! Glad to be here.
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David Bartel's Lab @bartellab.bsky.social · 18/12/2024
Bartel Lab bids a fond farewell to our incredible lab manager, Asia Stefano. Wishing you all the best on your new adventures in the Rocky Mountains, Asia—thank you for the amazing time we shared together!
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David Bartel's Lab @bartellab.bsky.social · 18/12/2024
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