Biology subjects

Moersdorf, D.

Publications and source records attributed to Moersdorf, D..

5 recordsLinked to original sources

bioRxiv2026

Kinetic logic of uridylation-mediated RNA decay

3'-terminal uridylation marks structured non-coding RNAs for cytoplasmic decay, yet how uridylation is quantitatively coupled to exonucleolytic degradation remains unclear. Here, we dissect the kinetic logic of uridylation-mediated RNA surveillance in Drosophila melanogaster. Using biochemical reconstitution together with high-throughput enzymology and quantitative modeling, we show that the terminal uridylyl transferase Tailor generates discrete oligo(U) intermediates through product-dependent kinetic tuning, while co-substrate promiscuity suppresses sustained processivity under physiological nucleotide conditions. Massively parallel binding and decay assays further reveal how the 3'-to-5' exoribonuclease Dis3l2 selectively degrades Tailor-primed RNAs by integrating 3'-proximal uridine content and defined 3'-end accessibility--features encoded by short, kinetically tuned oligo(U) intermediates centered on four nucleotides--to enable productive threading of RNA substrates along an extended RNA-binding path to the catalytic site. Together, our findings establish a quantitative framework in which uridylation encodes decay competence through transient RNA 3'-end states that are matched to the mechanistic requirements for decay. HighlightsO_LIThe TUTase Tailor kinetically tunes uridylation to generate short, discrete oligo(U) intermediates C_LIO_LIMixed nucleotide availability suppresses sustained processive uridylation C_LIO_LIDis3l2 decodes 3'-proximal uridine content and end accessibility to commit RNAs to decay C_LIO_LIShort oligo(U) tails encode RNA decay competence through transient RNA 3'-end states C_LI

biochemistry↗

bioRxiv2024

A whole-body atlas of non-graded BMP signaling activity in a sea anemone

BMP signaling is responsible for the second body axis patterning in Bilateria and in the bilaterally symmetric members of the bilaterian sister clade Cnidaria - corals and sea anemones. However, medusozoan cnidarians (jellyfish, hydroids) are radially symmetric, and yet their genomes contain BMP signaling components. This evolutionary conservation suggests that BMP signaling must have other functions not related to axial patterning, which keeps BMP signaling components under selective pressure. To find out what these functions might be, we generated a detailed whole-body atlas of BMP activity in the sea anemone Nematostella. In the adult polyp, we discover an unexpected diversity of domains with BMP signaling activity, which is especially prominent in the head, as well as across the neuro-muscular and reproductive parts of the gastrodermis. In accordance, analysis of two medusozoan species, the true jellyfish Aurelia and the box jellyfish Tripedalia, revealed similarly broad and diverse BMP activity, supporting the versatile nature of the BMP pathway across anthozoan and medusozoan Cnidaria.

developmental biology↗

bioRxiv2024

Chordin-mediated BMP shuttling patterns the secondary body axis in a cnidarian

BMP signaling patterns secondary body axes throughout Bilateria and, strikingly, in the bilaterally symmetric corals and sea anemones - members of the bilaterian sister clade Cnidaria. It has been suggested that the secondary, "directive" axis in the sea anemone Nematostella vectensis requires Chordin-mediated "shuttling" of BMP ligands, like in Drosophila or frog, however, an alternative "local inhibition" model is also possible. To choose between these two options, we generated localized Chordin sources in the Chordin morphant background and showed that in the presence of BMP ligands in Nematostella, mobile Chordin is necessary and sufficient to establish a peak of BMP signaling at the side of the embryo opposing the Chordin source. In contrast, membrane-tethered Chordin-CD2 promotes weak BMP signaling within the Chordin-CD2 source. These results provide the first mechanistic evidence for BMP shuttling in a cnidarian and suggest that BMP shuttling may have been functional in the cnidarian-bilaterian ancestor.

developmental biology↗

bioRxiv2022

β-catenin-dependent endomesoderm specification appears to be a Bilateria-specific co-option

Endomesoderm specification based on a maternal {beta}-catenin signal and axial patterning by interpreting a gradient of zygotic Wnt/{beta}-catenin signalling was suggested to predate the split between Bilateria and their evolutionary sister Cnidaria. However, in Cnidaria, the roles of {beta}-catenin signalling in both these processes have not been proven directly. Here, by tagging the endogenous {beta}-catenin protein in the sea anemone Nematostella vectensis, we show that the oral-aboral axis in a cnidarian is indeed patterned by a gradient of {beta}-catenin signalling. Unexpectedly, in a striking contrast to Bilateria, Nematostella endoderm specification takes place opposite to the part of the embryo, where {beta}-catenin is translocated into the nuclei. This suggests that {beta}-catenin-dependent endomesoderm specification is a Bilateria-specific co-option, which may have linked endomesoderm specification with the subsequent posterior-anterior patterning.

developmental biology↗

bioRxiv2022

Single-molecule tracking of Nodal and Lefty in live zebrafish embryos supports hindered diffusion model

The influential hindered diffusion model postulates that the global movement of a signaling molecule through an embryo is affected by local tissue geometry and binding-mediated hindrance, but these effects have not been directly demonstrated in vivo for any signaling molecule. Nodal and Lefty are a prime example of an activator-inhibitor signaling pair whose different global diffusivities are thought to arise from differential hindrance. Here, we used single-molecule tracking of Nodal and Lefty to directly probe the tenets of the hindered diffusion model on the nanoscale. We visualized individual fluorescently-tagged Nodal and Lefty molecules in developing zebrafish embryos using reflected light-sheet microscopy. Single-particle tracking revealed molecules in three states: molecules diffusing in extracellular cavities, molecules diffusing within cell-cell interfaces, and molecules bound to cell membranes. While the diffusion coefficients of molecules were high in extracellular cavities, mobility was reduced and bound fractions were higher within cell-cell interfaces; counterintuitively, molecules nevertheless accumulated in cavities. Using agent-based simulations, we identified the geometry of the extracellular space as a key factor influencing the accumulation of molecules in cavities. For Nodal, the fraction of molecules in the bound state was larger than for Lefty, and individual Nodal molecules had binding times of tens of seconds. Together, our single-molecule measurements and simulations provide direct support for the hindered diffusion model in a developing embryo and yield unprecedented insights into the nanometer to micrometer scale transport mechanisms that together lead to macroscopic signal dispersal and gradient formation.

biophysics↗