A5030997361- Cancer-related molecular mechanisms research
- RNA Research and Splicing
- RNA modifications and cancer
- RNA regulation and disease
- Plant and Fungal Interactions Research
- Nuclear Structure and Function
- MicroRNA in disease regulation
- Circular RNAs in diseases
- Cancer Research and Treatments
- Genetics, Aging, and Longevity in Model Organisms
- Graphene and Nanomaterials Applications
- Microtubule and mitosis dynamics
- Virus-based gene therapy research
- Neuroendocrine regulation and behavior
- RNA Interference and Gene Delivery
- Cellular transport and secretion
- Cellular Mechanics and Interactions
- Pluripotent Stem Cells Research
- Trace Elements in Health
- Conducting polymers and applications
- Receptor Mechanisms and Signaling
- Congenital heart defects research
- CRISPR and Genetic Engineering
- Histone Deacetylase Inhibitors Research
- Birth, Development, and Health
Weizmann Institute of Science
2012-2024
Abstract Chromodomain helicase DNA binding protein 2 ( Chd2 ) is a chromatin remodeller implicated in neurological disease. Here we show that Chaserr , highly conserved long noncoding RNA transcribed from region near the transcription start site of and on same strand, acts concert with CHD2 to maintain proper expression levels. Loss mice leads early postnatal lethality homozygous mice, severe growth retardation heterozygotes. Mechanistically, loss substantially increased mRNA levels, which...
How can cells sense their own size to coordinate biosynthesis and metabolism with growth needs? We recently proposed a motor-dependent bidirectional transport mechanism for axon length cell sensing, but the nature of motor-transported signals remained elusive. Here, we show that mRNA localization regulates neuronal cycling size. found RNA-binding protein nucleolin is associated importin β1 in axons. Perturbation association kinesins reduces its levels axons, concomitant reduction axonal...
The number of known long noncoding RNA (lncRNA) functions is rapidly growing, but how those are encoded in their sequence and structure remains poorly understood. NORAD (noncoding activated by DNA damage) a recently characterized, abundant, highly conserved lncRNA that required for proper mitotic divisions human cells. acts the cytoplasm antagonizes repressors from Pumilio family bind at least 17 sites spread through 12 repetitive units sequence. Here we study sequences repeats, identify...
Only a small portion of human long non-coding RNAs (lncRNAs) appear to be conserved outside mammals, but the events underlying birth new lncRNAs in mammals remain largely unknown. One potential source is remnants protein-coding genes that transitioned into lncRNAs. We systematically compare lncRNA and loci across vertebrates, estimate up 5% mammalian are derived from lost genes. These have specific characteristics, such as broader expression domains, set them apart other Fourteen sequence...
Size homeostasis is fundamental in cell biology, but it not clear how large cells such as neurons can assess their own size or length. We examined a role for molecular motors intracellular length sensing. Computational simulations suggest that spatial information be encoded by the frequency of an oscillating retrograde signal arising from composite negative feedback loop between bidirectional motor-dependent signals. The model predicts decreasing either both anterograde signals should...
Chromatin modifications play a key role in regulating gene expression during development and adult physiology. Histone acetylation, particularly H3K27ac, is associated with increased activity of regulatory elements such as enhancers promoters. However, the regulation machinery that write, read, erase this modification remains poorly understood. In particular, SIN3A-HDAC1 complex possesses histone deacetylase activity, yet it commonly resides at active regions. Here, we study BAHCC1, large...
Heterozygous loss of function mutations in the CHD2 gene, encoding for chromodomain helicase DNA-binding protein 2, are associated with severe childhood-onset epilepsy, global developmental delay, and autistic features. Here, we characterized behavioral epileptic phenotypes a mouse model harboring frameshift truncating mutation Chd2 gene (Chd2WT/m Chd2m/m mice). Genetic background dramatically affected phenotypes. While no were observed on pure C57BL/6J background, crossing these mice onto...
Long noncoding RNAs (lncRNAs) are expressed in many brain circuits and types of neurons; nevertheless, their functional significance for normal functions remains elusive. Here, we study the central nervous system Silc1, an lncRNA have shown previously to be important neuronal regeneration peripheral system. We found that Silc1 is rapidly strongly induced hippocampus upon exposure novelty required efficient spatial learning. production induction Sox11 (its cis-regulated target gene)...
Long noncoding RNAs (lncRNAs) have been shown to play important roles in gene regulatory networks acting early development. There has rapid turnover of lncRNA loci during vertebrate evolution, with few human lncRNAs conserved beyond mammals. The sequences these rare deeply are typically not similar each other. Here, we characterize HOXA-AS3 and HOXB-AS3, produced from the central regions HOXA HOXB clusters. Sequence-similar orthologs both found multiple species there is evident sequence...
Long non-coding RNAs (lncRNAs) are implicated in a plethora of cellular processes, but an in-depth understanding their functional features or mechanisms action is currently lacking. Here we study Meteor, lncRNA transcribed near the gene encoding EOMES, pleiotropic transcription factor various processes throughout development and adult tissues. Using wide array perturbation techniques, show that elongation through Meteor locus required for Eomes activation mouse embryonic stem cells, with...
Abstract Social anxiety disorder is characterized by a persistent fear and avoidance of social situations, but available treatment options are rather unspecific. Using an established mouse conditioning (SFC) paradigm, we profiled gene expression chromatin alterations after the acquisition extinction within septum, brain region important for behaviors. Here, particularly focused on successful versus unsuccessful outcome training, which corresponds to responsive resistant patients in clinics....
Abstract Genomic loci adjacent to genes encoding for transcription factors and chromatin remodelers are enriched long non-coding RNAs (lncRNAs), but the functional importance of this enrichment is largely unclear. Chromodomain helicase DNA binding protein 2 ( Chd2 ) a remodeller with various reported functions in cell differentiation damage response. Heterozygous mutations human CHD2 have been implicated epilepsy, neurodevelopmental delay, intellectual disability. Here we show that Chaserr ,...
Abstract Long noncoding RNAs (lncRNAs) are expressed in many brain circuits and neuronal types, but their significance to normal functions has remained largely unknown. Here, we study the central nervous system of Silc1 , a lncRNA previously showed be important for neuroregeneration peripheral system. We found that is rapidly strongly induced upon stimulation hippocampus required efficient spatial learning. production induction Sox11 (its cis-regulated target gene) throughout CA1-CA3 regions...