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

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...

biorxiv.org

Our work investigating mRNA 3' UTRs that trigger target-directed miRNA degradation is now published! genesdev.cshlp.org/content/earl...

David Bartel's Lab@bartellab.bsky.social · 9mo ago

Check out the latest work from our lab, led by Daniel Lin and Lara Elcavage: www.biorxiv.org/content/10.1... (1/3)

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

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...

tinyurl.com

David Bartel's Lab@bartellab.bsky.social · 7mo ago

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)

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...

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)

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...

We are looking for a postdoc to work on mechanisms of #RNA decay in cancer using #cryoEM with #nanobodies and #minibinders! Please RT

Check our latest collaboration with the Kleaveland Lab (kleavelandlab.org), led by Joanna Stefano and Lara Elcavage: academic.oup.com/nar/article/... (1/2)

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)

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...

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...

wi.mit.edu

Check out the latest work from our lab, led by Daniel Lin and Lara Elcavage: www.biorxiv.org/content/10.1... (1/3)

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...

biorxiv.org

Check out the latest work from our lab, led by Arash Latifkar @ara-latifkar.bsky.social , www.biorxiv.org/content/10.1...

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...

biorxiv.org

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)

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...

biorxiv.org

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...

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...

nature.com

Check out the latest study from our lab, led by Coffee Xiang (@coffeebond007.bsky.social) www.nature.com/articles/s41... (1/2)

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 ...

nature.com

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...

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...

biorxiv.org

Don’t miss this Q&A with Dr. Michelle Frank (@michelle-frank.bsky.social), an awesome postdoc in our lab!

Whitehead Institute@whiteheadinstitute.bsky.social · last yr.

Our latest Postdoc Q&A features Michelle Frank from the Bartel lab. Michelle is interested in how the brain balances the ability to learn new things with the need for maintaining stable connections. wi.mit.edu/news/meet-wh... #WhiteheadPostdocProfiles @bartellab.bsky.social

Check out the latest study from our lab, led by @mhall98.bsky.social : www.biorxiv.org/content/10.1... (1/2)

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

Seychelle Vos@voslab.org · 2y ago

Our collaborative AGO2 work with @bartellab.bsky.social is published! Abdallah and Peter used cryo-EM and biochemistry to determine the structure of AGO2 in a slicing competent conformation with a fully paired RNA. Read more about it here: tinyurl.com/AGO2-slicing

Check out our latest paper in collaboration with @voslab.org on the cryo-EM structure of slicing by human AGO2: tinyurl.com/AGO2-slicing

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.

tinyurl.com

Seychelle Vos@voslab.org · 2y ago

Our collaborative AGO2 work with @bartellab.bsky.social is published! Abdallah and Peter used cryo-EM and biochemistry to determine the structure of AGO2 in a slicing competent conformation with a fully paired RNA. Read more about it here: tinyurl.com/AGO2-slicing

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!