A5006337159- RNA modifications and cancer
- Genetics, Aging, and Longevity in Model Organisms
- Cancer-related gene regulation
- RNA and protein synthesis mechanisms
- RNA Research and Splicing
- Mitochondrial Function and Pathology
- Cancer-related Molecular Pathways
- Epigenetics and DNA Methylation
- Circadian rhythm and melatonin
- Acute Myeloid Leukemia Research
- Multiple Myeloma Research and Treatments
- Biochemical Acid Research Studies
- Birth, Development, and Health
- Cancer-related molecular mechanisms research
- ATP Synthase and ATPases Research
- Axon Guidance and Neuronal Signaling
- Metabolism and Genetic Disorders
- HER2/EGFR in Cancer Research
- Diet and metabolism studies
- Biochemical and Molecular Research
- Cancer, Hypoxia, and Metabolism
- Coenzyme Q10 studies and effects
- Angiogenesis and VEGF in Cancer
- Hippo pathway signaling and YAP/TAZ
- Neuroblastoma Research and Treatments
University of Amsterdam
2018-2024
Amsterdam University Medical Centers
2018-2024
Emma Kinderziekenhuis
2019
Amsterdam UMC Location University of Amsterdam
2017-2018
Sanquin
2017
Hubrecht Institute for Developmental Biology and Stem Cell Research
2011-2015
University Medical Center Utrecht
2011-2015
Royal Netherlands Academy of Arts and Sciences
2011-2014
Utrecht University
2013
Institute of Cell Biology and Neurobiology
2008
Long noncoding RNAs (lncRNAs) form an abundant class of transcripts, but the function majority them remains elusive. While it has been shown that some lncRNAs are bound by ribosomes, also convincingly demonstrated these transcripts do not code for proteins. To obtain a comprehensive understanding extent to which bind we performed systematic RNA sequencing on ribosome-associated pools obtained through ribosomal fractionation and compared content with nuclear (non-ribosome bound) cytosolic...
Slowing down translation in either the cytosol or mitochondria is a conserved longevity mechanism. Here, we found non-interventional natural correlation of mitochondrial and cytosolic ribosomal proteins (RPs) mouse population genetics, suggesting translational balance. Inhibiting C. elegans through mrps-5 RNAi repressed translation. Transcriptomics integrated with proteomics revealed that this inhibition specifically reduced efficiency mRNAs required growth pathways while increasing stress...
Zebrafish carrying heterozygous mutations for 17 different ribosomal protein (rp) genes are prone to developing malignant peripheral nerve sheath tumors (MPNSTs), a tumor type that is seldom seen in laboratory strains of zebrafish. Interestingly, the same rare arises zebrafish homozygous loss-of-function point mutation suppressor gene p53. For these reasons, and because p53 widely known be mutated majority human cancers, we investigated status rp(+/-) MPNSTs. Using monoclonal antibodies...
Mutations in the daf‐2 gene of conserved Insulin/Insulin‐like Growth Factor (IGF‐1) pathway double lifespan nematode Caenorhabditis elegans . This phenotype is completely suppressed by deletion Forkhead transcription factor daf‐16. To uncover regulatory mechanisms coordinating this extension life, we employed a quantitative proteomics strategy with mutants comparison N2 and daf‐16; mutants. revealed remarkable longevity‐specific decrease proteins involved mRNA processing transport,...
Mutations affecting the ribosome lead to several diseases known as ribosomopathies, with phenotypes that include growth defects, cytopenia, and bone marrow failure. Diamond-Blackfan anemia (DBA), for example, is a pure red cell aplasia linked mutation of ribosomal protein (RP) genes. Here we show knock-down DBA-linked RPS19 gene induces cellular self-digestion process autophagy, pathway critical proper hematopoiesis. We also observe an increase autophagy in cells derived from DBA patients,...
The deregulation of metabolism is a hallmark aging. As such, changes in the expression metabolic genes and profiles amino acid levels are features associated with aging animals. We previously reported that most acids decline age Caenorhabditis elegans (C. elegans). Glycine, contrast, substantially accumulates C. elegans. In this study we show coupled to decrease gene enzymes important for glycine catabolism. further supplementation significantly prolongs lifespan, early adulthood its...
Significance Deregulated global mRNA translation is a feature of various cancers and considered important in oncogenic transformation. In colorectal cancer (CRC), the role most common driver mutations APC , KRAS SMAD4 TP53 on translational capacity are incompletely understood. Here, using mouse human intestinal organoids, we found that each mutation governs epithelial cell. Global linked to known hallmarks, including cell proliferation growth upon accumulation these mutations, posing...
The biogenesis of ribosomes and their coordination protein translation consume an enormous amount cellular energy. As such, it has been established that the inhibition either process can extend eukaryotic lifespan. Here, we used next-generation sequencing to compare ribosome-associated RNAs from normal strains Caenorhabditis elegans those carrying life-extending daf-2 mutation. We found a long noncoding RNA (lncRNA), transcribed telomeric sequence 1 (tts-1), on mutant. Depleting tts-1 in...
Mitochondrial form and function are closely interlinked in homeostasis aging. Inhibiting mitochondrial translation is known to increase lifespan C. elegans, accompanied by a fragmented network. However, whether this link between morphology causal longevity remains uncharacterized. Here, we show elegans that disrupting network blocking fission or fusion synergizes with reduced prolong stimulate stress response such as the unfolded protein response, UPRMT. Conversely, immobilizing through...
Abstract Abnormal gut motility is a feature of several mitochondrial encephalomyopathies, and mutations in genes such as TYMP POLG, have been linked to these rare diseases. The human genome encodes three DNA ligases, which only one, ligase III (LIG3), has splice variant crucial for health. We investigated the effect reduced LIG3 activity resulting dysfunction seven patients from independent families, who showed common occurrence dysmotility neurological manifestations reminiscent...
The congenital bone marrow failure syndrome Diamond-Blackfan anemia (DBA) is typically associated with variants in ribosomal protein (RP) genes impairing erythroid cell development. Here we report multiple individuals biallelic HEATR3 exhibiting failure, short stature, facial and acromelic dysmorphic features, intellectual disability. These destabilize a whose yeast homolog known to synchronize the nuclear import of RPs uL5 (RPL11) uL18 (RPL5), which are both critical for producing subunits...
Smoothened, a heptahelical membrane protein, functions as the transducer of Hedgehog signaling. The kinases that modulate Smoothened have been thoroughly analyzed in flies. However, little is known about how phosphorylation affects vertebrates, mainly, because residues, where phosphorylated are not conserved from Drosophila to vertebrates. Given its molecular architecture, signaling likely be regulated manner analogous G protein–coupled receptors (GPCRs). Previously, it has shown, arrestins...
Abstract Variants in ribosomal protein (RP) genes drive Diamond-Blackfan anemia (DBA), a bone marrow failure syndrome that can also predispose individuals to cancer. Inherited and sporadic RP gene variants are linked variety of phenotypes, including malignancy, with no anemia. Here we report an individual diagnosed DBA carrying variant the 5′UTR RPL9 (uL6). Additionally, two from family multiple cancer incidences missense variant. Analysis cells these reveals despite both driving pre-rRNA...
Diamond-Blackfan anemia (DBA) is a rare inherited bone marrow failure disorder linked predominantly to ribosomal protein gene mutations. Here the European DBA consortium reports novel mutations identified in
Diamond-Blackfan anemia (DBA) is characterized by hypoplastic anemia, congenital anomalies, and a predisposition for malignancies. Most of our understanding this disorder stems from molecular studies combined with extensive data input international patient registries.To create an overview the pediatric DBA population in Netherlands.Forty-three patients diagnosed all Dutch university hospitals were included study, their clinical genetic characteristics collected records.Congenital...
Mutations in ribosomal protein (RP) genes can result the loss of erythrocyte progenitor cells and cause severe anemia. This is seen patients with Diamond-Blackfan anemia (DBA), a pure red cell aplasia bone marrow failure syndrome that almost exclusively linked to RP gene haploinsufficiency. While mechanisms underlying cytopenia phenotype these mutations are not completely understood, it believed stabilization p53 tumor suppressor may induce apoptosis cells. In stark contrast, from zebrafish...