Thanks a lot Yasin!

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

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)!

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!

Thanks a lot!

While you’re here: also have a look at the great related work on LENG8 from YongshengShi’s lab: www.biorxiv.org/content/10.1...

Wonderful collaboration with @max2max.bsky.social in Clemen’s lab, @abugai.bsky.social and @lorenzoana.bsky.social in Torben’s lab. Impossible without the support from Plaschka/ Brennecke/ Jensen labs @viennabiocenter.bsky.social, @imbavienna.bsky.social, @impvienna.bsky.social (10/10)

In sum our work reveals that (m)RNA-clamped UAP56 not only promotes mRNA export by binding TREX-2 at the NPC. It can also be read out by the LENG8-PS module in PAXT to destine the RNA for decay. (9/x)

Perturbation of the LENG8–ZFC3H1 interface, or rapid depletion of either protein, leads to the upregulation of bona fide PAXT polyA-RNA targets. This demonstrates that the LENG8-PS module is functionally important for PAXT function. (8/x)

Alphafold reveals a conserved mode of interaction between LENG8 and the PAXT scaffolding subunit ZFC3H1, which we can validate in vivo. Thus, LENG8-PS constitutes a TREX-2-like module of PAXT. (7/x)

To our great surprise we found that LENG8-PS links to the ′Poly(A) tail exosome targeting (PAXT)’ connection, implicated in the degradation of polyadenylated nuclear RNA through the exosome. (6/x)

Turns out they do! Both additional complexes bind UAP56 in vitro, and, like TREX-2, stimulate the release of RNA from UAP56. Seems counter-productive for mRNA export. So, what is their function? (5/x)

Most eukaryotes harbor two additional, less characterized TREX-2 like complexes: LENG8-PS and SAC3D1-PS, which interestingly differ in their subcellular localization. What is their function, and do they also act on UAP56? (4/x)

In the final step of mRNA export UAP56 enables docking of the mRNP (mRNA+bound proteins) to TREX-2, which is anchored at the nuclear pore. TREX-2 in turn removes UAP56 from the mRNA, enabling the release of the mRNP from the nuclear pore and its shuttling to the cytoplasm. (3/x)

We previously suggested a model for a core mRNA nuclear export pathway, which centers on the action of the RNA clampase UAP56: www.biorxiv.org/content/10.1... (2/x)