The Shechner lab in UW Pharmacology. We study Noncoding RNAs and cellular architecture. He/His/Him. All comments are my own. @ShechnerLab.bsky.social
Seattle, WA
Based in United States
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🎨🧁 Celebrate RNA Day 2026 with creativity!
@RNASociety Junior Scientists are excited to announce the 2026 RNA Society Art & Baking Contests, proudly sponsored by @lexogen. Showcase your RNA-inspired visual art or culinary creations for a chance to win cash prizes!
🏆
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AWESOME CONFERENCE ALERT!!
I had an absolute blast at the Fusion “Genome Regulation Through RNA” meeting back in 2024, and psyched to see its upcoming return! Let’s geek out about all things Chromatin and RNA together, in Cancun!
Talk abstract deadline: 10/17
Details👇
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Hello RNA World! Ever wonder what's "talking to" your favorite transcript, but were too scared to ask? In our review in @CellReports, @FKHM and I highlight new RNA-focused tools for discovering RNA interactions across organizational scales. Checkit!
tinyurl.com/ydn6e3ac
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And that's a wrap (for now)! I hope you've enjoyed this thread and give our preprint a read. Let us know what you think! (30/30)
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Taken together, our data allow us to propose the first-ever model for the molecular architecture of a single-locus subnuclear compartment. This dramatically expands our understanding of the factory's functional scope, and its architectural disruption in DCM (24/30).
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This explains some of our observations in the factory transcriptome, since many pre-TTN-proximal transcripts are putative targets of pre-TTN-proximal RBPs. Thus, these RNAs may be recruited via their interactions with factory-resident proteins (23/30).
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In fact, nearly the entire pool of SAFB (an RBP and "nuclear matrix" factor) and of QKI (a splicing factor that's also mutated in DCM) are localized within TTN RNA factories! (22/30)
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The factory proteome reveals a remarkable compartment that integrates RNA biogenesis with chromatin compartmentalization. Tons of exciting chromatin regulators (cohesins; SAFBs), RBPs (QKI; SRSF's; ELAVL1) and, surprisingly, DNA repair factors (FEN1; APEX1; MCM's) (21/30).
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Factory localization also correlates with splicing efficiency, as TTN-proximal transcripts are more differentially spliced than other RNAs. Many alternative splicing events are defects (e.g. Retained Introns) specific to KO cells. Almost none are direct RBM20-targets (19/30).
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We next used O-MAP-Seq to map the TTN RNA factory transcriptome, revealing hundreds of RNAs that localize near nascent TTN in WT and ∆RBM20 cardiomyocytes. Few of these RNAs are encoded in TTN-proximal DNA loci, suggesting that they're localized post-transcriptionally (18/30).
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Surprisingly, in WT cells TID loci bear repressive chromatin marks, and TID-enclosed genes are lowly expressed. Upon RBM20 loss we see a modest, though significant uptick in expression, with downstream effects on the broader transcriptome (17/30).
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Strikingly, upon loss of the RMB20 splicing factor, all of these chromatin interactions disappear. This implies either that RBM20 is required to build the TTN RNA compartment, or alternatively, that RBM20 is needed to keep nascent TTN localized within that compartment. (16/30)
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With this in hand, we set out to systematically map the chromatin, RNAs, and proteins in the TTN RNA factory. We began by probing the factory's genomic interactions, using O-MAP-ChIP. This revealed scores of Mb-scale domains in both cis and trans. (14/30)
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To our delight, this yielded exceptionally precise biotinylation in both cell types: just two biotin foci—corresponding to the two alleles of nascent TTN. So, in the context of 2 meters of folded DNA, O-MAP can home in and affinity-tag a single-locus nuclear compartment! (13/30)
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As a test case, we chose a cardiomyocyte-specific "RNA factory" recently discovered by @berteroale and Chuck Murry. This factory forms around nascent pre-mRNAs encoding the giant protein Titin (TTN), and compartmentalizes the splicing factor RBM20, a key TTN regulator (10/30).
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We reasoned that we could adapt O-MAP to probe individual nuclear compartments by targeting the nascent transcripts contained therein. But how can we selectively probe these nascent transcripts (and avoid mature RNAs)? By targeting O-MAP to introns! (9/30)
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O-MAP is a nearly universal tool for RNA-targeted microenvironment-mapping. It uses FISH-like DNA oligos to localize the proximity-biotinylating enzyme HRP to a target RNA. HRP then biotinylates nearby molecules, enabling their discovery (8/30).
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Notably, few tools are available for the targeted biochemical characterization of single loci. If you want to dissect the "neighborhood" around an individual locus—unbiasedly discovering the nearby chromatin domains, RNAs, and proteins—you're in for a challenging time. (5/30)
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Over the past few decades, our field has developed many powerful tools for probing this compartmental architecture. But there are still core aspects of nuclear organization that remain almost impossible to interrogate by existing technologies. (4/30)
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It's my pleasure to present the next big preprint from SheqLab! An exciting application of our O-MAP platform that I hope will transform the study of nuclear architecture.
If you've ever wanted to dissect the subnuclear "neighborhood" around an individual locus, read on! (1/30)
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Just as @oligopain has wanted to probe single-locus proteomes for years now, it's long been a dream of mine to enable single RNA-targeted interaction discovery. I've got the receipts, too, Brian—here's a snap from my postdoc fellowship proposal, submitted [*mumble* ] years ago...
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Alas, the moment has come to bid farewell to our beloved summer student—the unstoppable Idriana Abinales! Idriana joined us through the UW BioSTEP program, and was an absolute rock star. Best of luck, Idriana!!
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(Got a bit caught up in the celebrations yesterday, so forgive my tardiness.)
Please join me in congratulating our newly-minted *Dr.* Evan Kania! Dr. Kania has done some truly beautiful work developing O-MAP into a tool for proving subnuclear architecture.
SO PROUD!!!
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Love that @RNASociety seems to have learned what I’ve known for years—that this is Evan Kania’s world; we’re all just living in it. :) Congrats, Evan!!! #RNA2023 #ProudPI
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Yeah, gly radicals are, in fact, radical. As a diversion, I’ll also mention the tandem Gly riboswitch—radical in its own way:
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It’s hard to argue with beautiful chemistry. Like, for example, genetically-encoded polypeptide synthesis. So beautiful.
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It should surprise no one that my congratulatory note to (Dr.) Ash was written in nucleoli.
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DUDES THIS JUST HAPPENED!
So excited to announce that my first student, (the Twitter-shy) Ashley Tsue, has successfully defended her thesis!! So incredibly proud of her and her work. CONGRATS, DR. TSUE!!!
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Being in SheqLab means you'd be part of the incredible community here at @UW! We're famous for our hyper-collaborative, hyper-innovative culture. Our lab really embraces this, forming tight collaborations throughout the community. You'd have a ton of support and mentorship. 9/
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We're small, but we're plucky—think of it as a "startup" atmosphere. Here, you'd get more direct mentorship, and more intellectual agency and ownership of your work than you'd get elsewhere. And... 8/
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Okay, so why choose SheqLab? We're an energetic, creative, tight-knit group of RNA nerds! My goal is to create a supportive, collaborative, and engaging atmosphere; to always put the needs of my trainees first. We strive to do great science, and to train great scientists. 7/
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The ability to dissect an RNA-mediated compartment in situ makes it possible for us to finally address like, a *bajillion* longstanding structural and mechanistic questions that have long plagued the field. And by "us," I mean *us*—you, your future labmates, and I.
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