Biology subjects

Herbst, J.

Publications and source records attributed to Herbst, J..

4 recordsLinked to original sources

bioRxiv2023

SPPiDDRs: a new gene family in dicot plants involved in DNA-Damage Response

Living organisms must maintain the integrity of their genome, and plants are not exempt. In plants, recognition of DNA damage converges at the transcription factor SOG1, a functional homolog of the animal p53 protein. SOG1 directly controls the expression of hundreds of genes and orchestrates a sophisticated network of signaling pathways termed DNA-damage response (DDR). Only recently, several long non-coding RNA (lncRNA) loci were identified to be upregulated by DNA damage, and only a handful have been confirmed to actively contribute to DDR. In this study, we focused on one locus annotated as lncRNA and found that it is strongly and quickly upregulated upon DNA damage and is a direct target of SOG1. Combining in silico and experimental analyses, we demonstrate that this locus was wrongly annotated as lncRNA and is in fact a gene coding for a short protein that targets peroxisomes. Consequently, we renamed this locus SHORT PEROXISOMAL PROTEIN INDUCED IN DNA-DAMAGE RESPONSE1 (SPPiDDR1). SPPiDDRs are well conserved and present in multiple copies across dicot genomes, with Arabidopsis containing two additional copies, SPPiDDR2 and SPPiDDR3. The AtSPPiDDR paralogs differ on the transcriptional level, SPPiDDR3 being the least active. SPPiDDR1 and SPPiDDR2 are both also induced by salt, a stress treatment known to indirectly induce DNA damage via oxidative stress. We show that these two genes act redundantly and inhibit plant growth in response to salt stress.

molecular biology↗

bioRxiv2023

The long non-coding RNA LINDA restrains cellular collapse following DNA damage in Arabidopsis thaliana

The genomic integrity of every organism is endangered by various intrinsic and extrinsic stresses. To maintain the genomic integrity, a sophisticated DNA damage response (DDR) network is activated rapidly after DNA damage. Notably, the fundamental DDR mechanisms are conserved in eukaryotes. However, knowledge about many regulatory aspects of the plant DDR is still limited. Important, yet little understood, regulatory factors of the DDR are the long non-coding RNAs (lncRNAs). In humans, 13 lncRNAs functioning in DDR have been characterized to date, whereas no such lncRNAs have been characterized in plants yet. By meta-analysis, we identified the long intergenic non-coding RNA induced by DNA damage (LINDA) that responds strongly to various DNA double-strand break-inducing treatments, but not to replication stress induced by mitomycin C. After DNA damage, LINDA is rapidly induced in an ATM- and SOG1-dependent manner. Intriguingly, the transcriptional response of LINDA to DNA damage is similar to that of its flanking hypothetical protein-encoding gene. Phylogenetic analysis of putative Brassicales and Malvales LINDA homologs indicates that LINDA lncRNAs originate from duplication of a flanking small protein-encoding gene followed by pseudogenization. We demonstrate that LINDA is not only needed for the regulation of this flanking gene, but also for fine-tuning of the DDR after the occurrence of DNA double-strand breaks. Moreover, {Delta}linda mutant root stem cells are unable to recover from DNA damage, most likely due to hyper-induced cell death. SIGNIFICANT STATEMENTWe unraveled the functional relevance of the first lncRNA within the DNA damage response network of Arabidopsis thaliana. This lncRNA, termed LINDA, is an important part of the DNA damage response network, as it is needed for accurate regulation of cell death and cell cycle progression.

plant biology↗

bioRxiv2022

Primary Cilia are WNT Transducing Organelles whose Biogenesis is Regulated by a WNTPP1 axis

WNT signalling is of paramount importance in development, stem cell maintenance, and disease. WNT ligands typically signal via receptor activation at the plasma membrane to induce {beta}-catenin-dependent gene activation. Here we show that in primary cilia, WNT receptors relay a WNT/GSK3 signal that {beta}-catenin-independently promotes ciliogenesis. Innovations supporting this conclusion are monitoring acute WNT co-receptor activation (phospho-LRP6) and identifying and mutating the LRP6 ciliary targeting sequence. Ciliary WNT signalling inhibits protein phosphatase 1 (PP1) activity, a negative regulator of ciliogenesis, by decommissioning GSK3-mediated phosphorylation of the PP1 regulatory inhibitor subunit PPP1R2. Accordingly, deficiency of WNT/GSK3 signalling by depletion of cyclin Y and cyclin-Y-like protein 1 induces widespread primary cilia defects in mouse embryonic neuronal precursors, kidney proximal tubules, and adult mice preadipocytes. We conclude that primary cilia are WNT PP1 signalling organelles. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=127 SRC="FIGDIR/small/519813v1_ufig1.gif" ALT="Figure 1"> View larger version (37K): org.highwire.dtl.DTLVardef@4e8f4dorg.highwire.dtl.DTLVardef@1a246f6org.highwire.dtl.DTLVardef@e0df10org.highwire.dtl.DTLVardef@154a139_HPS_FORMAT_FIGEXP M_FIG A Localized WNT PP1 Signalling Axis Promotes Ciliogenesis The WNT co-receptor LRP6 localizes to the ciliary membrane, where it is phospho-primed via a CCNY/L1-dependent CDK (not shown). WNT signalling inhibits GSK3 (not shown) and leads to inhibition of Protein phosphatase 1, a negative regulator of ciliogenesis. Right, CCNY/L1 deficiency disrupts the WNT PP1 signalling axis, leading to ciliary defects. C_FIG

cell biology↗

bioRxiv2017

Learning to perform auditory discriminations from observation is efficient but less robust than learning from experience

Social learning enables complex societies. However, it is largely unknown how insights obtained from observation compare with insights gained from trial-and-error, in particular in terms of their robustness. We use aversive reinforcement to train \"experimenter\" zebra finches to discriminate between auditory stimuli in the presence of an \"observer\" finch. We find that experimenters are slow to successfully discriminate the stimuli but immediately generalize their ability to a new set of similar stimuli. By contrast, observers subjected to the same task instantly discriminate the initial stimulus set, but require more time for successful generalization. Drawing upon machine learning insights, we suggest that observer learning has evolved to rapidly absorb sensory statistics without pressure to minimize neural resources, whereas learning from experience is endowed with a form of regularization that enables robust inference.

animal behavior and cognition↗