Biology subjects

Schröder, M.

Publications and source records attributed to Schröder, M..

3 recordsLinked to original sources

bioRxiv2026

The human DEAD-box protein DDX3X regulates host and viral mRNA translation during Sendai Virus infection

DDX3X is a multifunctional DEAD-box RNA helicase with important roles in translation initiation and antiviral innate immune signaling, yet it is currently unknown whether viral infection affects its interactions with host RNAs. Here, we define the transcriptome-wide binding landscape of endogenous DDX3X in Sendai virus-infected human cells using PAR-CLIP. We show that DDX3X maintains its preference for GC-rich, highly structured 5'UTR regions during infection, but acquires a distinct set of infection-induced targets, including IFNB1 and multiple interferon-stimulated genes. We demonstrate that DDX3X directly binds the IFNB1 5'UTR and promotes its translation, establishing a previously unrecognized post-transcriptional mechanism contributing to DDX3X-dependent IFN-{beta} production. We also evaluated DDX3Xs binding to SeV RNAs and concluded that DDX3X is likely not actively recruited by SeV or has a significant effect on its viral life cycle. Our findings add a novel dimension to DDX3Xs involvement in anti-viral immunity with implications for further therapeutic development of DDX3X inhibitors.

molecular biology↗

bioRxiv2025

Cell-stereotyped DNA repair outcomes are widespread during genome editing

Genome editing outcomes are governed by DNA repair pathways that vary with cell type and state. We developed scOUT-seq (single-cell Outcomes Using Transcript sequencing), a scalable approach that jointly profiles transcriptomes and matched multi-allelic editing outcomes ranging from homology directed repair (HDR) to inter-chromosomal translocations. We mapped editing outcomes in human CD34 hematopoietic stem and progenitor cells (HSPCs), mouse LSK HSPC equivalents, human upper airway organoids, and mouse multi-organ in vivo editing. Profiling 500,000 alleles across 74 cell types, scOUT-seq revealed that outcomes in most cell subtypes differ markedly from the bulk average. Various cell types shifted major repair classes, preferred different molecular sequences, and even enriched large structural variants, with distinctive patterns of allelic co-occurrence. Surprisingly, rare stem subtypes diverged from prevalent progenitors, and inhibitory neuron subtypes efficiently incorporated HDR alleles. These data suggest the potential for tailored therapeutic editing that may have been missed by bulk measurements.

genomics↗

bioRxiv2024

Nanobodies against the myelin enzyme CNPase as tools for structural and functional studies

2,3-cyclic nucleotide 3-phosphodiesterase (CNPase) is an abundant constituent of central nervous system non-compact myelin, frequently used as a marker antigen for myelinating cells. The catalytic activity of CNPase, the 3-hydrolysis of 2,3-cyclic nucleotides, is well characterised in vitro, but the in vivo function of CNPase remains unclear. CNPase interacts with the actin cytoskeleton to counteract the developmental closure of cytoplasmic channels that travel through compact myelin; its enzymatic activity may be involved in adenosine metabolism and RNA degradation. We developed a set of high-affinity nanobodies recognizing the phosphodiesterase domain of CNPase, and the crystal structures of each complex show that the five nanobodies have distinct epitopes. One of the nanobodies bound deep into the CNPase active site and acted as an inhibitor. Moreover, the nanobodies were characterised in imaging applications and as intrabodies, expressed in mammalian cells, such as primary oligodendrocytes. Fluorescently labelled nanobodies functioned in imaging of teased nerve fibers and whole brain tissue sections, as well as super-resolution microscopy. These anti-CNPase nanobodies provide new tools for structural and functional biology of myelination, including high-resolution imaging of nerve tissue.

biochemistry↗