Biology subjects

Steiner, E.

Publications and source records attributed to Steiner, E..

5 recordsLinked to original sources

bioRxiv2026

Universal 3D Motif dynamics in RNA: The A-minor Switch

A-minor motifs consist of adenosines docking into adjacent RNA minor grooves, are the most prevalent 3D interaction stabilizing RNA structures, and widely considered as being static. NMR spectroscopy reveals a secondary structure equilibrium of these motifs between engaged and disengaged states, which we term the A-minor switch. A switch in E.coli ribosome helix 44 consists of a sparsely populated, transient single-nucleotide register shift that sequesters adenosines from their 3D structural A-minor contacts. Mutational trapping of the NMR-defined, A-minor-engaged ground and-disengaged excited state, combined with cryo-electron microscopy, visualizes this dynamic switch mechanism. Additionally, A-minor switches were identified using secondary structure ensemble analysis and mutational trapping was found to impair bacterial growth, directly linking RNA dynamics and function. Because A-minor motifs are widespread in structured RNAs, these findings establish A-minor switches as a general regulatory layer between secondary structure dynamics and tertiary contacts, exposing a new therapeutic target class.

biophysics↗

bioRxiv2024

Effect of Alcohol and Cocaine Abuse on Neuronal and Non-Neuronal Cell Turnover in the Adult Human Hippocampus

Clinical studies on humans with a history of chronic abuse of alcohol or cocaine show cognitive impairments associated with hippocampal atrophy. Adult hippocampal neurogenesis is a process important for memory formation and has been shown to be impaired by alcohol and cocaine in rodent models. It has thus been suggested that a reduction in adult neurogenesis may contribute to cognitive dysfunctions seen in patients with abuse. In addition, reduced adult neurogenesis has been suggested to play a role in the pathology of addiction vulnerability. We have previously demonstrated persistent adult hippocampal neurogenesis throughout life by measuring 14C concentrations in genomic DNA, incorporated during cell division, in a mixed cohort of subjects. In this study, we use the same strategy to assess the extent of cell turnover of neuronal and non-neuronal cells in the hippocampus of humans with known history of alcohol and cocaine abuse and compare these with healthy controls. We find that there is significant neuronal and non-neuronal turnover in healthy controls, as well as in individuals with long term alcohol use orcocaine use. Using mathematical modelling, we compare the extent of cell turnover of neurons and non-neuronal cells and did not find any significant difference between healthy controls and the two addiction groups. While we cannot exclude scenarios of altered adult neurogenesis over shorter periods of time, our data does not support the theory of low neurogenesis as a mechanism of addiction vulnerability.

neuroscience↗

bioRxiv2022

Spatial transcriptomics of T and B cell receptors uncovers lymphocyte clonal dynamics in human tissue.

The spatial distribution of lymphocyte clones within tissues is critical to their development, selection, and expansion. We have developed Spatial Transcriptomics of VDJ sequences (Spatial VDJ), which maps immunoglobulin and TR antigen receptors in human tissue sections. Spatial VDJ captures lymphocyte clones matching canonical T, B, and plasma cell distributions in tissues and amplifies clonal sequences confirmed by orthogonal methods. We confirm spatial congruency between paired receptor chains, develop a computational framework to predict receptor pairs, and link the expansion of distinct B cell clones to different tumor-associated gene expression programs. Spatial VDJ delineates B cell clonal diversity, class switch recombination, and lineage trajectories within their spatial context. Taken together, Spatial VDJ captures lymphocyte spatial clonal architecture across tissues, which could have important therapeutic implications. One-Sentence SummarySpatial transcriptomics-based technology co-captures T and B cell receptors within their anatomical niche in human tissue.

immunology↗

bioRxiv2022

Targeting RNA:Protein Interactions with an Integrative Approach Leads tothe Identification of Potent YB-1 Inhibitors

RNA-binding proteins are promising targets for developing new molecules of therapeutic interest. Nevertheless, targeting RNA:Protein interfaces is hampered by the lack of methods able to detect these interactions in cells while being amenable to High Content Screening. Here, we adapt the microtubule bench assay to score small molecules targeting interactions of endogenous mRNA with a specific protein in cells and demonstrate its robustness by targeting YB-1 (YBX-1 gene), a mRNA-binding protein involved in cancer progression and resistance to chemotherapy. The implementation of an integrative approach led to the identification of 22 hits validated by NMR and MD simulations of which 11 were found to significantly interfere with the binding of mRNA to YB-1 in cells at low micromolar concentrations. One of our leads is P1, an FDA-approved PARP-1 inhibitor. This work shows the potential of our integrative approach and paves the way for the development of RNA:Protein Interaction inhibitors.

biophysics↗

bioRxiv2020

A conserved superlocus regulates above- and belowground root initiation

During plant post-embryonic growth new meristems and associated stem cells form in different development contexts in order to respond to environmental cues. While underground lateral roots initiate from designated cells in the main root, an unknown mechanism allows cells to bypass the root/shoot identity trajectory and generate shoot-borne-roots. Using single-cell profiling of tomato (Solanum lycoperiscum) stems we isolated a rare transient cell population that serve as progenitors for shoot-borne-root meristems. Analysis of this population identified a transcription factor required for the formation of shoot-borne-roots which we named SHOOT BORNE ROOTLESS (SBRL). Evolutionary analysis revealed that SBRL function is deeply conserved in angiosperms and that it arose as part of an ancient duplicated superlocus, only lost in root-less plants, containing both shoot-borne and lateral root initiation regulators. We propose that the ability to activate a common transition state with context-specific regulators allows the remarkable developmental plasticity found in plants. One Sentence SummaryHighly conserved superlocus of LBD genes, acting within an early transition identity, regulates shoot-borne and lateral root formation.

plant biology↗