Ulrich Hohmann

Thanks a lot!

LENG8 mediates RNA nuclear retention and degradation in eukaryotes In eukaryotes, incompletely processed and misprocessed mRNAs as well as numerous noncoding RNAs are retained in the nucleus and often degraded. However, the mechanisms for this critical quality contro...

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)

Molecular basis of polyadenylated RNA fate determination in the nucleus Eukaryotic genomes generate a plethora of polyadenylated (pA+) RNAs[1][1],[2][2], that are packaged into ribonucleoprotein particles (RNPs). To ensure faithful gene expression, functional pA+ RNPs, in...

How are RNAs sorted for export vs. degradation in the nucleus? In collaboration with @heick.bsky.social’s lab we (@clemensplaschka.bsky.social and @juliusbrennecke.bsky.social labs) discovered a direct mechanistic link between the export and decay machineries: www.biorxiv.org/content/10.1... (1/x)