A5006164198- RNA modifications and cancer
- Mitochondrial Function and Pathology
- Ubiquitin and proteasome pathways
- RNA Research and Splicing
- RNA and protein synthesis mechanisms
- Bacterial Genetics and Biotechnology
- Extracellular vesicles in disease
- Genomics, phytochemicals, and oxidative stress
- DNA Repair Mechanisms
- Connective tissue disorders research
- Acute Myeloid Leukemia Research
- Endoplasmic Reticulum Stress and Disease
- Folate and B Vitamins Research
- Cancer-related molecular mechanisms research
- Computational Drug Discovery Methods
- Genetics, Aging, and Longevity in Model Organisms
- Protein Structure and Dynamics
- Kawasaki Disease and Coronary Complications
- interferon and immune responses
- ATP Synthase and ATPases Research
- Cancer-related gene regulation
- Lipid metabolism and biosynthesis
- Immune cells in cancer
- Genetics and Neurodevelopmental Disorders
- CRISPR and Genetic Engineering
Institute of Biochemistry and Biophysics, Polish Academy of Sciences
2016-2025
Medical University of Białystok
2022-2025
Polish Academy of Sciences
2013-2019
University of Warsaw
2013-2016
FAM46C is one of the most frequently mutated genes in multiple myeloma. Here, using a combination vitro and vivo approaches, we demonstrate that encodes an active non-canonical poly(A) polymerase which enhances mRNA stability gene expression. Reintroduction into myeloma cell lines, but not its catalytically-inactive mutant, leads to broad polyadenylation stabilization mRNAs strongly enriched with those encoding endoplasmic reticulum-targeted proteins induces death. Moreover, silencing cells...
Abstract Intercellular communication within the bone marrow niche significantly promotes leukemogenesis and provides protection of leukemic cells from therapy. Secreted factors, intercellular transfer mitochondria receptor–ligand interactions have been shown as mediators this protection. Here we report that tunneling nanotubes (TNTs)—long, thin membranous structures, which identified a novel mode cross-talk—are formed in presence stroma mediate cellular vesicles to cells. Importantly,...
The GC skew in vertebrate mitochondrial genomes results synthesis of RNAs that are prone to form G-quadruplexes (G4s). Such RNAs, although mostly non-coding, transcribed at high rates and degraded by an unknown mechanism. Here we describe a dedicated mechanism degradation G4-containing which is based on cooperation between degradosome quasi-RNA recognition motif (qRRM) protein GRSF1. This prevents accumulation transcripts human mitochondria. In vitro reconstitution experiments show GRSF1...
Synapses are the regions of neuron that enable transmission and propagation action potentials on cost high energy consumption elevated demand for mitochondrial ATP production. The rapid changes in local energetic requirements at dendritic spines imply role mitochondria maintenance their homeostasis. Using global proteomic analysis supported with complementary experimental approaches, we show an essential pool proteins is locally produced synapse indicating protein biogenesis takes place to...
Abstract In mammals, m7G-adjacent nucleotides undergo extensive modifications. Ribose of the first or and second transcribed can be subjected to 2′-O-methylation form cap1 cap2, respectively. When nucleotide is 2′-O-methylated adenosine, it additionally modified N6,2′-O-dimethyladenosine (m6Am). Recently, crucial role in distinguishing between ‘self’ ‘non-self’ mammalian cells during viral infection was revealed. Here, we attempted understand impact cap methylations on RNA-related processes....
Abstract Over the recent years, fluorescence microscopy has seen substantial progress, transitioning from primarily qualitative analysis to a profoundly quantitative methodology, yet limitations in imaging depth and data quality persist due tissue opacity. Tissue optical clearing (TOC) methodologies were implemented overcome this hurdle, enabling of large samples such as entire murine organs. Further improvements, including expansion merge TOC benefits with improved resolution, converting...
Among numerous enzymes involved in RNA decay, processive exoribonucleases are the most prominent group responsible for degradation of entire molecules. The role mammalian cytoplasmic 3'-5' exonuclease DIS3L at organismal level remained unknown. Herein, we established knock-in and knock-out mouse models to study functions mice. mice is indeed a subunit exosome complex, disruption which leads severe embryo degeneration death soon after implantation. These changes could not be prevented by...
MGME1, also known as Ddk1 or C20orf72, is a mitochondrial exonuclease found to be involved in the processing of DNA (mtDNA) during replication. Here, we present detailed insights on role MGME1 mtDNA maintenance. Upon loss elongated 7S species accumulate owing incomplete 5' ends. Moreover, an 11-kb linear fragment spanning entire major arc genome generated. In contrast control cells, where molecules are detectable only after nuclease S1 treatment, persists MGME1-deficient cells. parallel,...
Research Article18 March 2019Open Access Source DataTransparent process Inhibition of proteasome rescues a pathogenic variant respiratory chain assembly factor COA7 Karthik Mohanraj Laboratory Mitochondrial Biogenesis, Centre New Technologies, University Warsaw, Poland ReMedy International Agenda Unit, Institute Molecular and Cell Biology, Search for more papers by this author Michal Wasilewski Corresponding Author [email protected] orcid.org/0000-0002-4890-5103 Cristiane Benincá MRC Biology...
Atherosclerosis, a common age-related disease, is characterized by intense immunological activity. Atherosclerotic plaque composed of endothelial cells, vascular smooth muscle cells (VSMCs), lipids and immune infiltrating from the blood. During progression VSMCs undergo senescence within secrete SASP (senescence-associated secretory phenotype) factors that can actively modulate microenvironment. We demonstrated senescent increased number extracellular vesicles (senEVs). Based on unbiased...
The exosome complex is a major eukaryotic exoribonuclease that requires the SKI for its activity in cytoplasm. In yeast, Ski7 protein links both complexes, whereas functional equivalent of has remained unknown human genome. Proteomic analysis revealed previously uncharacterized short splicing isoform HBS1L (HBS1LV3) long-sought factor linking and complexes humans. contrast, canonical variant, HBS1LV1, which acts as ribosome dissociation factor, does not associate with instead interacts mRNA...
During the winter months of 2020/2021 a wave multisystem inflammatory syndrome in children (MIS-C) emerged Poland. We present results nationwide register aiming to capture and characterise MIS-C with focus on severity determinants. The first Poland was notably high, hence our analysis involved 274 children. group 62.8% boys, median age 8.8 years. Besides one Asian, all were White. Overall, disease course not as severe previous reports, however. Pediatric intensive care treatment required for...
Chronic and acute myeloid leukemia evade immune system surveillance induce immunosuppression by expanding proleukemic Foxp3+ regulatory T cells (Tregs). High levels of immunosuppressive Tregs predict inferior response to chemotherapy, relapse, shorter survival. However, mechanisms that promote in leukemias remain largely unexplored. Here, we identify leukemic extracellular vesicles (EVs) as drivers effector Tregs. Using mouse model leukemia-like disease, found Rab27a-dependent secretion EVs...
Although encouraging results of adipose-derived stem cell (ADSC) use in wound healing are available, the mechanism action has been studied mainly vitro and animals. This work aimed to examine safety efficacy allogenic ADSCs human diabetic foot ulcer treatment, combination with analyses wound. Equal groups 23 participants each received fibrin gel or alone. The clinical effects were assessed at four time points: days 7, 14, 21 49. Material collected during debridement from a subset group was...
The water-soluble vitamin - B12, also known as cobalamin, plays a crucial role in cellular metabolism, particularly DNA synthesis, methylation, and mitochondrial functionality. Its de-ficiency can lead to hematological neurological disorders, however the manifestation of these clinical outcomes is relatively late. It leads difficulties its early diagnosis, often resulting development hidden subclinical cobalamin deficiency. Prolonged lack B12 con-dition may have severe consequences including...
Premature senescence, a death escaping pathway for cells experiencing stress, is conducive to aging and cardiovascular diseases. The molecular switch between senescent apoptotic fate remains, however, poorly recognized. Nrf2 an important transcription factor orchestrating adaptive response cellular stress. Here, we show that both human primary endothelial (ECs) murine aortas lacking signaling are but unexpectedly do not encounter damaging oxidative Instead, they exhibit markedly increased...
Photodynamic therapy (PDT) is a valuable treatment method for vulvar intraepithelial neoplasia (VIN). It allows the of multifocal disease with minimal tissue destruction. 5-Aminolevulinic acid (5-ALA) most commonly used prodrug, which converted in heme pathway to protoporphyrin IX (PpIX), an actual photosensitizer (PS). Unfortunately, not all patients treated PDT undergo complete remission. The main cause their failure resistance anticancer therapy. In many cancers, various treatments...
Innate immunity is the first line of host defense against pathogens. Here, through global transcriptome and proteome analyses, we uncover that newly described cytoplasmic poly(A) polymerase TENT-5 (terminal nucleotidyltransferase 5) enhances expression secreted innate effector proteins in Caenorhabditis elegans . Direct RNA sequencing revealed multiple mRNAs with signal peptide–encoding sequences have shorter tails tent-5 –deficient worms. Those are translated at endoplasmic reticulum where...
<title>Abstract</title> Leukemia cells residing in the bone marrow often exhibit resistance to tyrosine kinase inhibitors. Metabolic rearrangement of cancer has recently gained particular attention as a possible cause adaptation and insensitivity drug treatment. We demonstrated here that stromal directly transferred membrane vesicles together with proteins related tricarboxylic acid (TCA/Krebs) cycle leukemic cells. This transfer was dependent on direct cell-to-cell contact led increased...