iiinova — where your digital self keeps evolving

Ulrich Hohmann @hohmannulrich.bsky.social · 22/06/2026

Super cool to see the result of our collaborative work with @heick.bsky.social 's lab finally out! Shaped through many discussions with @abugai.bsky.social, @lorenzoana.bsky.social & @max2max.bsky.social, @juliusbrennecke.bsky.social & Clemens, trying to decipher LENG8's secrets!

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Marvin Tanenbaum @marvintanenbaum.bsky.social · 13/05/2026

For 40 years the 8-nt ‘Kozak Sequence’ was thought to mark sites of translation initiation. In a new study, we revise this model by identifying an ~80-nt sequence—the extended Translation Initiation Sequence (eTIS)— that guides ribosomes to correct start sites. 🧵 www.biorxiv.org/content/10.6...

biorxiv.org

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Laura Lorenzo Orts @lorenzoorts.bsky.social · 08/05/2026

We should all think twice before providing personal feedback on scientific presentations. For example, criticizing an accent is pointless. If you had difficulty understanding a presentation, suggest that the speaker slow down; don't point out their origin.

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Baptiste Rafanel @baptisterafanel.bsky.social · 06/05/2026

I'm super happy to finally see the paper published ! Check out the full story here: link.springer.com/article/10.1...

link.springer.com

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Biochemical Society @biochemsoc.bsky.social · 14/04/2026

Bridging the gap between biochemistry and developmental biology, we are excited to announce Laura Lorenzo Orts as a recipient of an Early Career Research Award in 2027! Laura's new lab focusses on understanding the mechanisms that activate mRNAs during early development.

Portrait of Dr Laura Lorenzo-Orts, Institute of Molecular Biology, Germany, recipient of the 2027 Biochemical Society Early Career Research Award.

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Biochemical Society @biochemsoc.bsky.social · 14/04/2026

We are so proud of all our Biochemical Society 2027 Award winners. Visit our website to find out more about all of the deserving recipients #BiochemAwards 🧪 ow.ly/mZ6O50YIGo8

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Peter Andersen @germline.bsky.social · 01/04/2026

Germ cells have their own versions of core transcription factors and fertility depends on them. We're hiring a PhD student to figure out how! 📢 Fly genetics + proteomics + genomics. Fully funded. Aarhus University 🇩🇰 Deadline May 1 👇 Please share with anyone who might be interested!

phd.nat.au.dk

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Kurianlab @kurianlab.bsky.social · 31/03/2026

Excited host @hohmannulrich.bsky.social from @imbmainz.bsky.social, along with @manuelkaulich.bsky.social Date: 07.04.2026 Time: 15:00 Venue: Haus 22 Seminar Room 1. (S22-1) Title: ‘Mechanistic insights into nuclear mRNA export and degradation’ @goetheuni.bsky.social @cpi-exstra.bsky.social

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Michael Hothorn @structplantbio.bsky.social · 23/03/2026

New method paper from Alberto Caregnato and former PhD student @hohmannulrich.bsky.social. A tailored crystallisation screen for plant receptor kinase ectodomains, with examples from our lab and from @cellsensing.bsky.social. Check it out: www.biorxiv.org/content/10.6...

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Julius Brennecke @juliusbrennecke.bsky.social · 19/03/2026

There has never been a better time to study functional and mechanistic biology at the organismal (!) level than now in the age of AlphaFold and CRISPR.

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Julius Brennecke @juliusbrennecke.bsky.social · 13/02/2026

The demystification of piRNA clusters if you wonder how cells generate piRNAs specifically against transposons & you are looking for a weekend read check out @86dominik.bsky.social's opus magna (or Dominik's great thread) a shared project with the one and only Rippei Hayashi, lab alumnus & friend

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Irene Beusch @pauletteoctopus.bsky.social · 11/02/2026

Do you want to understand how RNA #splicing decisions are made? We‘ve got a PhD position open for you (see 👇👇)!! Please share #RNAsky and RT! tinyurl.com/4ztu9cb9

tinyurl.com

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Institute of Molecular Biology (IMB) @imbmainz.bsky.social · 09/02/2026

Ulrich’s research will help advance our understanding of RNA biology & gene regulation, as well as how these mechanisms might be altered during viral infections & other diseases. @hohmannulrich.bsky.social comes from the @impvienna.bsky.social / @imbavienna.bsky.social www.imb.de/about-imb/ne...

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Laura Lorenzo Orts @lorenzoorts.bsky.social · 06/02/2026

Really excited to join IMB for this new scientific endeavour!

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Institute of Molecular Biology (IMB) @imbmainz.bsky.social · 06/02/2026

@lorenzoorts.bsky.social previously worked as a postdoctoral fellow at @impvienna.bsky.social in Austria. She will establish a new lab at IMB to investigate how mRNA translation is activated in the early embryo. Welcome to IMB Laura! 💐 Read more here: www.imb.de/about-imb/ne...

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Ulrich Hohmann @hohmannulrich.bsky.social · 06/01/2026

Very cool work! Reminiscent of how target engaged PIWI is selected from a vast pool of PIWI-piRNA complexes. Only target engaged PIWI is recognized by a GTSF1 protein and Maelstrom in the PIWI* complex. www.cell.com/molecular-ce... @juliusbrennecke.bsky.social @julsportell.bsky.social

piwi.read

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Jakob Farnung @jakobfarnung.bsky.social · 06/01/2026

When RNA Degradation 🤝 meets 🤝 Protein Degradation! tinyurl.com/E3TDMD In a collaboration of @bartellab.bsky.social and Schulman lab, we show that, in target-directed microRNA degradation (TDMD), 2-RNA-factors recruit an E3 ligase and induce the degradation of not only a protein but also RNA (1/5).

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Changwei YU @changweiyu.bsky.social · 22/12/2025

Very happy to share my postdoc work (on preprint), where we try to understand a long-standing transcription-silencing paradox, and uncovered a hidden RNA decay arm of nuclear piRNA pathway, see detailed threads quoted from @juliusbrennecke.bsky.social

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Ulrich Hohmann @hohmannulrich.bsky.social · 02/01/2026

Looking for a great first read for 2026? Look no further: Fantastic work spearheaded by my courageous colleague @changweiyu.bsky.social, with surprising findings not only for small RNA but also for exosome and gene expression aficionados

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Laura Lorenzo Orts @lorenzoorts.bsky.social · 14/12/2025

As 2025 comes to an end, it’s time for me to say good bye to my postdoc home during the past 6 years – the Pauli lab @pauligroup.bsky.social @impvienna.bsky.social

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Plaschka lab @plaschkalab.bsky.social · 21/11/2025

How does messenger RNA (mRNA) get out of the nucleus to become a protein? Eukaryotic mRNA is packaged, exported, and then translated in the cytoplasm. But how do these steps work? And what are open questions? Check out our new review for our take: www.annualreviews.org/content/jour... (1/3)

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Plaschka lab @plaschkalab.bsky.social · 21/11/2025

Messenger RNA is made in the nucleus before it is exported to the cytoplasm for translation. But how are only correctly made mRNAs chosen and remodeled in the nucleus for export? Our new paper investigates the nuclear events leading to human mRNA export. www.nature.com/articles/s41.... (1/4)

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Ulrich Hohmann @hohmannulrich.bsky.social · 19/11/2025

Lastly, I’m excited to join @imbmainz.bsky.social in 2026 to start my own lab. We'll explore new mechanisms in eukaryotic gene expression, leveraging ‘evolutionary play’ to uncover how regulation, repurposing, and hijacking shape RNA biology. tinyurl.com/y4x29ctt Thanks for reading! 20/20

Ulrich Hohmann @hohmannulrich.bsky.social · 19/11/2025

And of course also a big ‘Thank you!’ to colleagues and support at @imbavienna.bsky.social, @impvienna.bsky.social, @viennabiocenter.bsky.social and for funding to @boehringerglobal.bsky.social, @erc.europa.eu, and my postdoc fellowships from @embo.org and Marie Skłodowska-Curie Actions 19/

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Ulrich Hohmann @hohmannulrich.bsky.social · 19/11/2025

This was a quite a journey, and would not have been possible without my mentors @juliusbrennecke.bsky.social & Clemens, my colleagues in the Brennecke and @plaschkalab.bsky.social labs, and the institutional support at the @viennabiocenter.bsky.social. 18/

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Ulrich Hohmann @hohmannulrich.bsky.social · 19/11/2025

Finally, we test the linearity of this model through IP-MS of UAP56 mutants. If we perturb TREX-2 binding (UAP56 mutant M1) -> UAP56 accumulates on mRNPs. THO binding (M2) -> UAP56 depletes from mRNPs. THO+TREX-2 binding (M3) -> mirrors loss of THO binding alone. 17/

Immunoprecipitations followed by quantitative mass spectrometry of wildtype (wt) or three UAP56 protein mutants probe the mRNA export model. An experiment schematic is shown on the left. The top heatmap (greyscale) shows log2 fold-changes in protein enrichment of wildtype UAP56 versus a control. The bottom heatmaps (blue-white-red scale), show fold-changes of three UAP56 mutants versus wildtype UAP56: UAP56 mutant M1 (D49R, L51D), UAP56–TREX-2 binding mutant; M2 (F336E, R339D), UAP56–THO-binding mutant; M3, combined UAP56 THO- & TREX-2-binding mutant (M1 & M2). The enrichment of GANP in UAP56 mutant M2 is likely due to the binding of free nuclear UAP56 mutant M2 protein to TREX-2.

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Ulrich Hohmann @hohmannulrich.bsky.social · 19/11/2025

Taken together, we find that UAP56 is an “mRNP packaging mark”, that controls important aspects of the nuclear events of the mRNA export pathway: disassembly of TREX, docking of the mRNP at the NPC, and release into the NPC. 16/

A general model for mRNA nuclear export.
The ATPase and mRNA clampase UAP56 is a central molecular switch that steers human mRNAs through mRNP packaging and multivalent TREX–mRNP globule assembly (I), TREX–mRNP disassembly and the formation of export-competent UAP56–mRNPs, assisted by the multivalent protein SARNP (II and III), mRNP docking (IV), and mRNP release (IV) at the NPC via TREX-2. Loading of the mRNA export factor NXF1–NXT1 onto mRNPs may occur in the nucleoplasm or at the NPC, initiating mRNP nuclear export.

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Ulrich Hohmann @hohmannulrich.bsky.social · 19/11/2025

We can visualize this TREX-2 activity also directly: we bead-immobilize UAP56–ADP-Pi–RNA complexes. Incubation with TREX-2 releases UAP56 from the RNA. In contrast, as expected, the THO complex does not have any effect on clamped UAP56. 15/

UAP56 RNA-unclamping assay. Bead-immobilized 15 nucleotide poly-Uridine RNA is incubated with UAP56 and ATP to form UAP56–ADP-Pi–RNA complexes, which are then challenged with recombinant THO or TREX-2M complexes. Bead-remaining UAP56–ADP-Pi–RNA complexes are analyzed by SDS-PAGE (Coomassie-staining).

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Ulrich Hohmann @hohmannulrich.bsky.social · 19/11/2025

A highly conserved ‘wedge’ loop of the TREX-2 subunit GANP binds the nucleotide, which is still bound to UAP56’s RecA1 lobe (unusual for an open DExD ATPase). In vitro ATPase assays show a dramatic stimulation of UAP56’s ATPase rate by TREX-2. So TREX-2 promotes RNA release from UAP56! 14/

TREX-2 stimulates the apparent ATPase rate of UAP56 in vitro (left). Plotted are the ATPase rates of the RecA2P56–TREX-2 ‘M’ mixtures. The addition of TREX-2 accelerates UAP56’s apparent ATPase rate 57 fold.
The GANP wedge binding mimics the ATP-binding pocket in clamped UAP56 (middle and right). Shown are the UAP56-bound nucleotide and nucleotide base stacking residues in sticks representation, colored by heteroatom. In the UAP56–TREX-2 structure the adenine moiety of the non-hydrolyzable ATP analogue forms stacking interactions with F65 in the UAP56 RecA1 lobe and the GANP wedge residue R678 (middle). In clamped UAP56 (PDB ID 8ENK) (Xie et al., 2023), the adenine base of bound ADP stacks with F65 of UAP56’s RecA1 lobe and F381 of the RecA2 lobe (right).

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Ulrich Hohmann @hohmannulrich.bsky.social · 19/11/2025

However, to complete export, the mRNP must subsequently be released again from TREX-2. How does this happen? To our surprise, in our cryo-EM structure of the UAP56–TREX-2 complex UAP56 was not in an RNA-bound, closed conformation, but instead open?! 13/

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Ulrich Hohmann @hohmannulrich.bsky.social · 19/11/2025

In cells we show: the identified interfaces are critical for cell viability. In addition, perturbing the UAP56–TREX-2 interaction leads to mRNA export defects, as assessed (amongst other assays) through polyA-FISH in human K562 cells with a knockout-rescue setup for the TREX-2 subunit PCID2. 12/

Mutation of the UAP56 NTD–PCID2 interface in PCID2 leads to the accumulation of nuclear poly(A) RNA. Shown are representative cells (left; z-projection) and the ratios of the nucleo-cytoplasmic (N/C) poly(A) RNA FISH signal (right) after the depletion of endogenous PCID2 or GANP for 16 h, or upon the depletion and rescue of endogenous PCID2 with wildtype or mutant PCID2 constructs, M1 and M2. M1, PCID2 NTD-binding mutant (K374D, K388D); M2, PCID2 GANP-binding mutant (D356R, A365F). Scale bar = 10 μm; Four replicates per condition, with >70 cells per replicate. Pairwise significance testing was performed using two-sided Welch t-tests, with FDR correction for multiple testing, where *** P<0.001.

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Ulrich Hohmann @hohmannulrich.bsky.social · 19/11/2025

Could TREX-2 be a landing pad at the NPC for UAP56-bound, export ready mRNPs? Biochemically we show that UAP56 does indeed bind TREX-2 and solved a cryo-EM strcture of the complex. This revealed a role for the conserved UAP56 NTD in TREX-2 binding. 11/

Cartoon representation of a Cryo-EM structure of human UAP56–TREX-2 middle region (TREX-2 ‘M’:GANP residues 602-942, PCID2, SEM1).

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Ulrich Hohmann @hohmannulrich.bsky.social · 19/11/2025

Besides known UAP56 interactors we find some novel ones. Among them: GANP and PCID2, two subunits of the TREX-2 complex. A big surprise to us! TREX-2 (sharing only its name with TREX) is involved in mRNA export and bound to the basket of the nuclear pore complex (NPC)… 10/

AlphaFold2 Multimer in silico protein interaction screen to identify novel UAP56 interactors. All UAP56–candidate predictions are shown (circles) and ranked by the average interface prediction TM score (interface pTM). Known and several novel predicted interactors are highlighted in colors.

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Ulrich Hohmann @hohmannulrich.bsky.social · 19/11/2025

So: TREX disassembly yields mature, export-ready mRNPs, marked by clamped UAP56. Could clamped UAP56 be a molecular mark controlling final steps of nuclear export? To find new UAP56 interactors we used AlphaFold2 Multimer to screen the nuclear UAP56 interactome. 9/

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Ulrich Hohmann @hohmannulrich.bsky.social · 19/11/2025

Remarkably, SARNP disassembles THO-UAP56 in the presence of ATP and RNA in vitro. And in endogenous mRNPs? We purified endogenous TREX-bound mRNPs. Again, a minimal SARNP construct (including the UCM) could dissociate the mRNP from THO. 8/

Native TREX–mRNP disassembly assay. Experiment schematic (left) and massspectrometry results (right, heatmap) of bead-retained mRNP-associated proteins after adding the ALYREF N-UBM, SARNP UCM-1, or an UCM-1–N-UBM fusion. The heatmap is colored according to the log2 fold-change compared to the buffer control, after normalizing to mean THO complex subunit levels.

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Ulrich Hohmann @hohmannulrich.bsky.social · 19/11/2025

Is RNA clamping of UAP56 regulated? We identify SARNP as a ‘clamping factor’. It has a motif we named ‘UCM’, which binds adjacent to the newly identified N-UBM binding site on UAP56. N-UBM and UCM cooperatively enhance UAP56’s affinity for RNA, this might aid directionality of mRNP remodelling. 7/

Structural model of a clamped UAP56–ADP-Pi–RNA complex bound to SARNP and ALYREF. The model was obtained by superposing structures of clamped UAP56–ADP-BeF3–RNA (PDB-ID 8ENK) (Xie et al., 2023), open UAP56–ALYREF N- and C-UBMs (Fig. 1), and a UAP56–SARNP UCM-1 AlphaFold2 Multimer prediction.

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Ulrich Hohmann @hohmannulrich.bsky.social · 19/11/2025

Upon RNA clamping UAP56 hydrolyses ATP, and the resulting UAP56–ADP-Pi–RNA complexes are remarkably stable, for example persisting in size exclusion chromatography experiments. This suggests that UAP56 can be ‘deposited’ on the mRNA as a maturation mark. 6/

Size exclusion chromatography of UAP56 and ATP with or without 15 nucleotide poly-Uridine RNA. UV-traces at 280 nm (black) and 260 nm (grey) are shown.

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Ulrich Hohmann @hohmannulrich.bsky.social · 19/11/2025

Could the conformational change in UAP56 between its open and its RNA-clamped state play a role? Turns out it does: Open UAP56 binds THO, RNA-clamped UAP56 has no measurable affinity! This suggests that clamping of UAP56 releases THO from the mRNP. 5/

Representation of open (unclamped) and RNA clamped UAP56. Shown alongside are Grating Coupled Interferometry derived binding curves for open and RNA clamped UAP56 vs. the THO complex. Isolated, open UAP56 binds the tetrameric THO complex with nano molar affinity (top), whereas RNA-clamped, closed UAP56–ATP–RNA has no measurable THO complex affinity (bottom).

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Ulrich Hohmann @hohmannulrich.bsky.social · 19/11/2025

We found that UAP56 binds to the two known UAP56-binding motifs (UBMs) in mRNP export adapters, such as ALYREF, in distinct ways. The C-UBM binds the previously known site on UAP56’s RecA1 lobe, but, unexpectedly, the N-UBM binds a distinct site on the RecA2 lobe. 4/

Cartoon representation of the cryoEM structure of a human TREX complex. UAP56 binds ALYREF through an N- and C-UBM at its respective RecA2 and RecA1n domains, and is in an open conformation, primed to clamp onto the associated segment of putative mRNA.

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Ulrich Hohmann @hohmannulrich.bsky.social · 19/11/2025

THO binds to maturing mRNPs (=mRNA+proteins), directing them into the mRNA export pathway. Yet THO must again dissociate, to allow for subsequent steps in export. How? The connection between mRNP and THO is the DExD-box ATPase UAP56, which binds to UBM motifs in mRNP export adapters (like ALYREF).3/

Cartoon representation of the cryo-EM structure of the endogenous human TREX complex (THO+UAP56+ALYREF) bound to an mRNP

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Ulrich Hohmann @hohmannulrich.bsky.social · 19/11/2025

mRNA nuclear export is a key step in eukaryotic gene expression. While the key players had been discovered over the past decades, the structural basis for how these proteins remodel mRNAs for nuclear export was unclear. 2/

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Ulrich Hohmann @hohmannulrich.bsky.social · 19/11/2025

Finally out in @nature.com! We uncovered a mechanistic framework for a general and conserved mRNA nuclear export pathway. www.nature.com/articles/s41.... 1/

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Ulrich Hohmann @hohmannulrich.bsky.social · 12/10/2025

Shout-out also to my wonderful colleagues in the Hothorn / Brennecke / Plaschka labs, as well as to the great environment and many colleagues at the University of Geneva, @viennabiocenter.bsky.social, @impvienna.bsky.social, @imbavienna.bsky.social

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Ulrich Hohmann @hohmannulrich.bsky.social · 12/10/2025

This would have been impossible without the amazing support from my PhD mentor @structplantbio.bsky.social, and my postdoc mentors @juliusbrennecke.bsky.social and Clemens Plaschka (@plaschkalab.bsky.social)!

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Ulrich Hohmann @hohmannulrich.bsky.social · 12/10/2025

Apply to the PhD program until Oct. 16th: www.imb.de/students-pos... More info on our future lab: www.imb.de/research/our... I’m looking forward to future endeavours in Mainz and exciting science to happen!

imb.de

Apply to the IPP

IMB Mainz

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Ulrich Hohmann @hohmannulrich.bsky.social · 12/10/2025

Thrilled to share that I’ll be joining @imbmainz.bsky.social in February 2026 to start my own group! We will explore new mechanisms in eukaryotic gene expression, leveraging ‘evolutionary play’ to uncover how regulation, repurposing, and hijacking shape RNA biology. PhD positions available!

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