Matthew Taliaferro

20 years ago are you serious?

Maybe I’ll keep tidying my own dataframes a little while longer.

The registration deadline for this wonderful meeting is approaching! Be sure to reserve your spot before March 10!

We’re excited to kick off 2026 with a joint meeting with the London RNA Club, featuring Mary Ann Allen and
@loverna.bsky.social!

🗓 Wednesday, February 25, 2026
⏰ 10:00 AM MST
📍 Zoom: please RSVP here for link: docs.google.com/forms/d/e/1F...

Supported by @rnasociety.bsky.social

Excited to share that this work is now published in its final form!

link.springer.com/article/10.1...

TDP-43 directly inhibits mRNA accumulation in neurites through modulation of mRNA stability - The EMBO Journal The subcellular localization of many mRNAs to neuronal projections allows neurons to efficiently and rapidly react to spatially restricted external cues. However, for most of these RNAs, the mechanism...

A mechanism for controlling mRNA localization to neuronal projections:
Daniel Dominguez, Matthew Taliaferro @jmtali.bsky.social and collaborators implicated ALS-linked TDP-43 as inhibitor of mRNA accumulation in neurites, possibly by promoting their decay
link.springer.com/article/10.1...

Join us in Porto for the forefront of RNA localization & local translation research! Registration is live!

My favourite meeting! Highly recommend registering for this one...

Registrations are due March 10, and both travel grants and dependent care grants are available. We look forward to seeing you in Portugal next summer!

meetings.embo.org/event/26-rna...

Announcing the 2026 edition of the EMBO workshop on RNA localization and local translation! This meeting will be held June 30 - July 4 near Porto, Portugal. Come for exciting updates in the field from both established investigators and trainees. See the link below for details!

How does one review his paper if he’s infallible?

New @prelights.bsky.social post ! I'm happy to highlight @jmtali.bsky.social lab latest preprint prelights.biologists.com/highlights/t...

We received notice that two F31s were terminated and submitted another F31 application two hours later. We keep on trucking, I guess.

Thanks Junjie!

Two updates with this project! First, this work is now published here: academic.oup.com/nar/article/...

Second, our software for identifying 8-oxoguanosine via RNAseq, PIGPEN, is now installable via bioconda: anaconda.org/bioconda/pig...

Bartolomeo Tagliaferro Sr. (1530-1601) - Find a... Born in Venice, Italy. Lived in various parishes in London until his death. Buried September 22, 1601, at St. Olave's Hart Street London. Married Joane Lanier/Lanyer on 1 JAN 1583 at St. Michaels, C...

Thanks Mike! I looked into this a while back, and I am a direct patrilineal descendant of this guy: www.findagrave.com/memorial/133.... Blacksmithing skills got lost somewhere along the way though.

TDP-43 directly inhibits RNA accumulation in neurites through modulation of RNA stability The subcellular localization of hundreds of RNAs to neuronal projections allows neurons to efficiently and rapidly react to spatially restricted external cues. However, for the vast majority of these ...

www.biorxiv.org/content/10.1...

Thanks Manny!

TDP-43 directly inhibits RNA accumulation in neurites through modulation of RNA stability The subcellular localization of hundreds of RNAs to neuronal projections allows neurons to efficiently and rapidly react to spatially restricted external cues. However, for the vast majority of these ...

www.biorxiv.org/content/10.1...

...the unnecessary loss of time, expertise, and money. In short, it is the opposite of increased efficiency.

...from the people in the lab doing the experiments to the staff that oversee compliance with regulations to ensure thoughtful stewardship of hard earned taxpayer money. Wild, unpredictable changes to the system result in turnover of these key personnel, resulting in...

Finally, one more comment given recent events. All this work, which may one day lead to cures for ALS, relies not just on federal funding, but on a *stable* funding system, including indirect costs. Those funds pay the salaries of people that are indispensable to this effort...

If we replace wildtype TDP-43 with an ALS mutant TDP-43, we again see that the same RNAs become aberrantly neurite-enriched. So this could be happening in ALS patient cells, but whether it makes contributions to patient phenotypes is another question for another day.

Does any of this have anything to do with ALS? Maybe. We see the same RNA localization defects happening in primary mouse motor neurons and human iPS-derived motor neurons upon TDP-43 loss.

260mers that drove TDP-43-dependent localization and were bound by TDP-43 in vitro also showed TDP-43-dependent changes in stability, directly linking all three processes. All of these qualities were eliminated if TDP-43 motifs in the 260mers were eliminated.

OK, so *how* is TDP-43 doing this? TDP-43 negatively regulates RNA stability and recent work has linked RNA localization and stability. So is this what's going on? To test this we measured the stability of the same ~10k reporters with and without TDP-43 using SLAM-seq.

Sure enough, 260mers that have TDP-43-dependent localization activity are directly bound by TDP-43, and mutation of TDP-43 motifs within them abrogates both binding and activity.

OK so we have 260mers that have TDP-43-dependent RNA localization activity. But are they actually bound by TDP-43? To test this, we measured the TDP-43 affinity for the exact same ~10k 260mer RNAs in vitro, allowing us to directly relate binding to activity.

So what distinguishes these bound/active motifs from unbound/inactive motifs? Secondary structure. Bound motifs are significantly more single-stranded. We can predict whether or not a TDP-43 motif regulates RNA localization simply by looking at its secondary structure character.

Only some TDP-43 motifs are actually occupied by TDP-43 in cells, and only those motifs made RNAs TDP-43-sensitive. Further, mutation of those motifs abolished activity, while mutation of other non-occupied motifs had no effect.