Dave Shechner
@shechnerlab.bsky.social
The Shechner lab in UW Pharmacology. We study Noncoding RNAs and cellular architecture, and we build “democratized” RNA-focused chemical biology and genomics tools.
He/His/Him. Almost cartainly not D.B. Cooper
ShechnerLab.org
He/His/Him. Almost cartainly not D.B. Cooper
ShechnerLab.org
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👇
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👇
September 19, 2025 at 11:44 PM
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👇
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👇
A day late but STILL IMPORTANT
August 2, 2025 at 4:14 PM
A day late but STILL IMPORTANT
Hello! Ever wonder what's "talking to" your favorite transcript, but were too scared to ask? In our review in @cp-cellreports.bsky.social, @mardakheh.bsky.social and I highlight new RNA-focused tools for discovering RNA interactions across organizational scales. Checkit!
tinyurl.com/ydn6e3ac
tinyurl.com/ydn6e3ac
June 30, 2025 at 9:15 PM
Hello! Ever wonder what's "talking to" your favorite transcript, but were too scared to ask? In our review in @cp-cellreports.bsky.social, @mardakheh.bsky.social and I highlight new RNA-focused tools for discovering RNA interactions across organizational scales. Checkit!
tinyurl.com/ydn6e3ac
tinyurl.com/ydn6e3ac
Aw, yeah! It’s en-dash time, people!
December 17, 2024 at 3:32 AM
Aw, yeah! It’s en-dash time, people!
Just updated my phone OS, and apparently the calendar doubles as a karyotype now?
November 30, 2024 at 6:40 PM
Just updated my phone OS, and apparently the calendar doubles as a karyotype now?
Oh, it’s ON now. Welcome, welcome, @lippilab.bsky.social!
November 29, 2024 at 11:26 PM
Oh, it’s ON now. Welcome, welcome, @lippilab.bsky.social!
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)
November 21, 2024 at 1:37 AM
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)
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).
November 21, 2024 at 1:35 AM
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).
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).
November 21, 2024 at 1:35 AM
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).
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)
November 21, 2024 at 1:35 AM
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)
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).
November 21, 2024 at 1:34 AM
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).
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).
November 21, 2024 at 1:34 AM
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).
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).
November 21, 2024 at 1:33 AM
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).
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).
November 21, 2024 at 1:33 AM
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).
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)
November 21, 2024 at 1:32 AM
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)
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)
November 21, 2024 at 1:32 AM
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)
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)
November 21, 2024 at 1:31 AM
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)
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).
November 21, 2024 at 1:30 AM
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).
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)
November 21, 2024 at 1:30 AM
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)
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).
November 21, 2024 at 1:29 AM
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).
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)
November 21, 2024 at 1:28 AM
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)
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)
November 21, 2024 at 1:28 AM
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)
This project was driven by the unstoppable Evan Kania (now *Dr.* Kania) and aided by an incredible team of collaborators—including @dschweppe.bsky.social, and @oligopain.bsky.social, @shaoenong, @berteroale, and Chuck Murry. Find the preprint below. Now let's jump it! (2/30)
tinyurl.com/yurzfyjp
tinyurl.com/yurzfyjp
November 21, 2024 at 1:27 AM
This project was driven by the unstoppable Evan Kania (now *Dr.* Kania) and aided by an incredible team of collaborators—including @dschweppe.bsky.social, and @oligopain.bsky.social, @shaoenong, @berteroale, and Chuck Murry. Find the preprint below. Now let's jump it! (2/30)
tinyurl.com/yurzfyjp
tinyurl.com/yurzfyjp
It's my great 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)
If you've ever wanted to dissect the subnuclear "neighborhood" around an individual locus, read on! (1/30)
November 21, 2024 at 1:27 AM
It's my great 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)
If you've ever wanted to dissect the subnuclear "neighborhood" around an individual locus, read on! (1/30)