Refine
Year of publication
Language
- English (62)
Has Fulltext
- yes (62) (remove)
Is part of the Bibliography
- no (62)
Keywords
- Proteomics (3)
- complexome profiling (3)
- mitochondria (3)
- Aging (2)
- Calpain (2)
- Complex I (2)
- NADPH oxidase (2)
- Podospora anserina (2)
- Reactive oxygen species (2)
- aging (2)
- bioenergetics (2)
- long non-coding RNA (2)
- mitochondrial disease (2)
- A/D transition (1)
- AAA+ disaggregase (1)
- Activities of daily living (1)
- Adult neurogenesis (1)
- Alternative oxidase (1)
- Apoptosis (1)
- Ataxia (1)
- Autoimmune vasculopathy (1)
- Autophagy (1)
- BIAM switch assay (1)
- BIAM-switch (1)
- BPTF (1)
- Behavior (1)
- Biochemistry (1)
- Brain (1)
- Calcium calmodulin kinase (1)
- Cardiac infarction (1)
- Cardiology (1)
- Cardiomyopathy (1)
- Cell signalling (1)
- Chaperone (1)
- Chemical modification (1)
- Chemiluminescence (1)
- ClpB (1)
- Complex II (1)
- Complexome profiling (1)
- Conformational change (1)
- Cortex (1)
- DNA Damage (1)
- DNA methylation (1)
- Data visualization (1)
- Database (1)
- ERAL1 (1)
- Endothelial cell (EC) (1)
- Endothelial cells (1)
- Endothelial protein C receptor (1)
- FAIR (1)
- Flavin mononucleotide (1)
- G3BP1 (1)
- HARS2 (1)
- HSP (hereditary spastic paraplegia) (1)
- Heart (1)
- Heart transplantation (1)
- Hig1 (1)
- Hypoxia inducible factor (1)
- ICAM-1 (1)
- IL-1β (1)
- Innate immunity (1)
- IntelliCage (1)
- Isoforms (1)
- KLHL11 (1)
- LARS2 (1)
- Lactic acidosis (1)
- Leukodystrophy (1)
- LncRNA - long noncoding RNA (1)
- Long non-coding RNAs (1)
- Lucigenin (1)
- Lysosome (1)
- MEIS homeodomain protein (1)
- MTRNR1 (1)
- Mass spectrometry (1)
- Membrane assays (1)
- Microparticles (1)
- Mitochondria (1)
- Mitochondrial ROS (1)
- Mitochondrial amino acid tRNA synthetases (1)
- Mitochondrial complex I (1)
- Mitochondrial disease (1)
- Mitochondrial disorder (1)
- Mitochondrial dysfunction (1)
- N-hydroxysuccinimide (1)
- N471D strumpellin knock-in mice (1)
- NADH:ubiquinone oxidoreductase (1)
- NDUFA6 (1)
- NDUFAF8 (1)
- NURF (1)
- Neonatal (1)
- Neurodegeneration (1)
- Nitric oxide (1)
- Nox (1)
- Nox4 (1)
- OXPHOS (1)
- POLG (1)
- PRLTS3 (1)
- Parkinson’s disease (1)
- Perrault syndrome (1)
- Play (1)
- Pleasure (1)
- Post-translational modifications (1)
- Posttranslational modification (1)
- Prognosis (1)
- Progranulin (1)
- Protein complex (1)
- Protein tyrosine modification (1)
- RNA Biology (1)
- RNA turnover (1)
- RNA, long noncoding (1)
- Rapamycin (1)
- Rcf1 (1)
- Redox modification (1)
- Redoxin (1)
- Release of mtDNA and mtRNA (1)
- Respiratory chain (1)
- Reverse electron transfer (1)
- SDH (1)
- SPG8 (1)
- Senescence (1)
- Starvation (1)
- Stem cell (1)
- Stroke (1)
- Stroke genetics (1)
- Subventricular zone (1)
- Superoxide (1)
- TRIM25 (1)
- TWINKLE (1)
- TWNK (1)
- Tissue-specificity (1)
- Transcription factor (1)
- Treatment (1)
- Ubiquitin (1)
- Ubiquitin ligase (1)
- Vitamin (1)
- WASH complex subunit 5 (1)
- adaptive cardiac remodelling (1)
- alternative oxidase (1)
- alternative splicing (1)
- angiogenesis (1)
- aortic aneurysm (1)
- assembly (1)
- ataxia (1)
- atherosclerosis (1)
- cGAS-STING (1)
- cancer metastases (1)
- cardiac ischaemia‐reperfusion (1)
- cardiolipin (1)
- cardiovascular disease (1)
- caspase-2 (1)
- chemotherapy resistance (1)
- colon carcinoma cells (1)
- complex I (1)
- complex I deficiency (1)
- crista junction (1)
- cristae (1)
- cytochrome c oxidase (complex IV) (1)
- data repositories (1)
- diabetes mellitus (1)
- electron transport chain (1)
- epigenomics (1)
- gene expression (1)
- glioblastoma (1)
- hypertension, pulmonary (1)
- i-AAA protease (1)
- intrinsic apoptosis (1)
- ischemia (1)
- leukodystrophy (1)
- long non-coding RNAs (1)
- macrophage (1)
- mass spectrometry (1)
- matrix metalloproteinase (1)
- membrane protein complex (1)
- membrane structure (1)
- metabolomics (1)
- molecular diagnosis (1)
- mouse (1)
- neovascularization, physiologic (1)
- nonsense-mediated mRNA decay (1)
- polyunsaturated fatty acid (1)
- proliferation (1)
- protein complexes (1)
- protein quality control (1)
- protein–protein interaction (1)
- proteomics (1)
- reactive oxygen species (1)
- remodeling (1)
- smooth muscle cell (1)
- strumpellin (1)
- temperature (1)
- therapeutics (1)
- tight junctions (1)
- vascular disease (1)
- vascular integrity (1)
- vascular remodeling (1)
- yeast (1)
Institute
Tight control over transcription factor activity is necessary for a sensible balance between cellular proliferation and differentiation in the embryo and during tissue homeostasis by adult stem cells, but mechanistic details have remained incomplete. The homeodomain transcription factor MEIS2 is an important regulator of neurogenesis in the ventricular–subventricular zone (V-SVZ) adult stem cell niche in mice. We here identify MEIS2 as direct target of the intracellular protease calpain-2 (composed of the catalytic subunit CAPN2 and the regulatory subunit CAPNS1). Phosphorylation at conserved serine and/or threonine residues, or dimerization with PBX1, reduced the sensitivity of MEIS2 towards cleavage by calpain-2. In the adult V-SVZ, calpain-2 activity is high in stem and progenitor cells, but rapidly declines during neuronal differentiation, which is accompanied by increased stability of MEIS2 full-length protein. In accordance with this, blocking calpain-2 activity in stem and progenitor cells, or overexpression of a cleavage-insensitive form of MEIS2, increased the production of neurons, whereas overexpression of a catalytically active CAPN2 reduced it. Collectively, our results support a key role for calpain-2 in controlling the output of adult V-SVZ neural stem and progenitor cells through cleavage of the neuronal fate determinant MEIS2.
Long non-coding RNAs (lncRNAs) contribute to cardiac (patho)physiology. Aging is the major risk factor for cardiovascular disease with cardiomyocyte apoptosis as one underlying cause. Here, we report the identification of the aging-regulated lncRNA Sarrah (ENSMUST00000140003) that is anti-apoptotic in cardiomyocytes. Importantly, loss of SARRAH (OXCT1-AS1) in human engineered heart tissue results in impaired contractile force development. SARRAH directly binds to the promoters of genes downregulated after SARRAH silencing via RNA-DNA triple helix formation and cardiomyocytes lacking the triple helix forming domain of Sarrah show an increase in apoptosis. One of the direct SARRAH targets is NRF2, and restoration of NRF2 levels after SARRAH silencing partially rescues the reduction in cell viability. Overexpression of Sarrah in mice shows better recovery of cardiac contractile function after AMI compared to control mice. In summary, we identified the anti-apoptotic evolutionary conserved lncRNA Sarrah, which is downregulated by aging, as a regulator of cardiomyocyte survival.