A5064344552- RNA Research and Splicing
- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- Developmental Biology and Gene Regulation
- Genomics and Chromatin Dynamics
- Mitochondrial Function and Pathology
- CRISPR and Genetic Engineering
- Genetics, Aging, and Longevity in Model Organisms
- Neurogenesis and neuroplasticity mechanisms
- Neurogenetic and Muscular Disorders Research
- Amyotrophic Lateral Sclerosis Research
- ATP Synthase and ATPases Research
- Genetics and Neurodevelopmental Disorders
University Medical Center Hamburg-Eppendorf
2018-2024
Universität Hamburg
2018-2024
École Polytechnique Fédérale de Lausanne
2020-2024
Institute for Stem Cell Biology and Regenerative Medicine
2019
The RNA-binding protein TDP-43 is heavily implicated in neurodegenerative disease. Numerous patient mutations TARDBP, the gene encoding TDP-43, combined with data from animal and cell-based models, imply that altered RNA regulation by causes Amyotrophic Lateral Sclerosis Frontotemporal Dementia. However, underlying mechanisms remain unresolved. Increased cytoplasmic levels diseased neurons suggest a possible role this cellular compartment. Here, we examined impact on translation of...
Genes implicated in translation control have been associated with autism spectrum disorders (ASDs). However, some important genetic causes of autism, including the 16p11.2 microdeletion, bear no obvious connection to translation. Here, we use proteomics, genetics, and assays cultured cells mouse brain reveal altered mediated by loss kinase TAOK2 deletion models. We show that associates translational machinery functions as a brake phosphorylating eukaryotic elongation factor 2 (eEF2)....
Translation depends on messenger RNA (mRNA)-specific initiation, elongation, and termination rates. While translation elongation is well studied in bacteria yeast, less known higher eukaryotes. Here we combined ribosome transfer (tRNA) profiling to investigate the relations between rates, (aminoacyl-) tRNA levels, codon usage mammals. We modeled codon-specific dwell times from profiling, considering pair interactions sites. In mouse liver, model revealed site- that differed those as pairs of...
Protein synthesis is crucial for maintaining synaptic plasticity and signalling. Here we have attempted to understand the role of RNA binding proteins, Fragile X Mental Retardation (FMRP) Moloney Leukemia Virus 10 (MOV10) protein in N-Methyl-D-Aspartate Receptor (NMDAR) mediated translation regulation. We show that FMRP required downstream NMDAR stimulation MOV10 key specificity factor this process. In rat cortical synaptoneurosomes, association with Argonaute 2 (AGO2) forms inhibitory...
To adapt mitochondrial function to the ever-changing intra- and extracellular environment, multiple stress response (MSR) pathways, including unfolded protein (UPRmt), have evolved. However, how signal is sensed relayed UPRmt transcription factors, such as ATFS-1 in Caenorhabditis elegans, remains largely unknown. Here, we show that a panel of vacuolar H+-ATPase (v-ATPase) subunits target rapamycin complex 1 (TORC1) activity are essential for cytosolic relay induction UPRmt. Mechanistically,...
In the neocortex, functionally distinct areas process specific types of information. Area identity is established by morphogens and transcriptional master regulators, but downstream mechanisms driving area-specific neuronal specification remain unclear. Here, we reveal a role for RNA-binding proteins in defining cytoarchitecture. Mice lacking Pum2 or overexpressing human TDP-43 show apparent 'motorization' layers IV V primary somatosensory cortex (S1), characterized dramatic expansion cells...
Abstract Microdeletions in the 16p11.2 region of human genome are frequently associated with autism spectrum disorders (ASDs), but how these genomic rearrangements cause ASD remains unclear. Here, we reveal that TAOK2β, a protein isoform encoded by TAOK2 gene located locus, regulates mRNA translation. To identify key functional interaction partners performed proteomic screening from Neuro-2a (N2a) cells, mouse cortices, and cultured neurons. This revealed translation factors as major class...